J Pediatr Adolesc Gynecol (2006) 19:39–43

Case Report

Anaplastic Carcinoma Arising in an Ovarian MucinousCystadenocarcinoma in a 17-Year-Old Female

Joseph Vella, BS1, Bernadette Cracchiolo, MD2, and Debra S. Heller, MD3

1New Jersey Medical School, Newark, New Jersey; 2Departments of Obstetrics, Gynecology, & Women’s Health;3Pathology & Laboratory Medicine, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA

Abstract. Background: Anaplastic carcinoma arisingwithin a mucinous ovarian neoplasm is rare, with onlyabout 30 reported cases. Reported cases have given a broadage range, ranging from 17 to 72 years of age, but occur-rence in adolescents is exceptional, with only a few casesreported.

Case: We report a case of anaplastic carcinoma arisingin a mucinous cystadenocarcinoma in a 17-year-old femalewho presented with severe abdominal pain, an unusualsymptom for an ovarian malignancy in the postmenopausalpatient, but not in the adolescent. The patient had wide-spread metastases at the time of presentation, consistentwith the aggressive behavior of this neoplasm.

Conclusions: This case illustrates that, although rare,epithelial ovarian malignancy is in the differential diagnosisof abdominal pain in an adolescent.

Key Words. Ovarian neoplasmsdMucinousneoplasmsdCarcinoma

Introduction

Patients with mucinous neoplasms of the ovary maypresent with symptoms such as abdominal distentionand vague pelvic or abdominal pain of a few monthsduration. Many are first detected on routine gyneco-logic examination. Significant pain is an unusual pre-senting symptom in an older woman, but is not rare inan adolescent. Solid mural nodules within mucinousneoplasms of the ovary are rare. The types of nodulesthat have been reported to occur in both benign andmalignant mucinous neoplasms include sarcoma-likenodules, true sarcomas, and anaplastic carcinomas.

Address correspondence to:Debra S. Heller, MD, Dept of Pathology-UH/E158, UMDNJ-New Jersey Medical School, PO Box 1709,

Newark, NJ, 07101; E-mail: hellerds@umdnj.edu

� 2006 North American Society for Pediatric and Adolescent GynecologyPublished by Elsevier Inc.

It can be a histological challenge to distinguish thesedifferent mural lesions from one another, as in addi-tion to the similarities between sarcoma-like nodulesand true sarcoma, anaplastic carcinomas can have sar-comatous features. It is important, however, to estab-lish the nature of the nodules in these cases, as thesarcoma-like mural nodules are benign, in comparisonto true sarcoma and anaplastic carcinoma.1 We pres-ent the case of a 17-year-old female who presentedwith abdominal pain, and was found to have anaplas-tic carcinoma arising in a mucinous carcinoma,extremely rare in this age group.

Case Report

The patient was a 17-year-old G0 who presented witha chief complaint of right-side abdominal pain of sev-eral months duration. Previous to transfer to our insti-tution, she had presented to another hospital withsevere pain. A urine pregnancy test was reportedly pos-itive. Prior to transfer, a transvaginal ultrasound andcomputed tomography of the pelvis were performed.The computerized tomography revealed a "large con-glomerate of complex enhancing mass lesions originat-ing within the pelvis and extending into the lowerabdomen without evidence of free fluid in the pelvisor cul-de-sac." These findings correlated with the trans-vaginal ultrasound done earlier in the day.

On presentation to our institution, the patient wasin mild distress and reported a pain score of 4 outof 10. She denied nausea, vomiting, diarrhea, or con-stipation. She reported dyspareunia of a few weeksduration. Physical examination was significant fora scaphoid abdomen with mild right lower quadranttenderness to deep palpation. On bimanual and limitedrectovaginal examination there was a 6–8 cm massextending into the pelvis and deviating the right cervi-covaginal fornix, which was tender.

1083-3188/06/$22.00doi:10.1016/j.jpag.2005.11.005

40 Vella et al: Anaplastic Carcinoma of the Ovary

The following tumor markers were drawn withelevated findings: LDH5 1334 u/l, BHCG5 325 mIU/ml, CA 125 5 1576 U/ml, and CEA 5 392.5 ng/ml.AFP was within normal limits. She was offered anexploratory laparotomy with surgical cytoreduction asdeemed necessary based on frozen section analysis.The preoperative differential diagnosis included a dys-germinoma (high b-HCG and LDH) or a mixed germcell tumor, choriocarcinoma, embryonal carcinoma orpolyembryoma (high b-HCG). Less likely was animmature teratoma (which usually presents with AFPelevations). Thought to be even less likely was anepithelial tumor, which rarely presents in this age groupdespite the elevated CA125.

Intraoperatively, both ovaries were involved andfixed in the pelvis with tumor extension into the rightobturator fossa encasing the iliac vessels. She under-went TAH-BSO, omentectomy, suboptimal debulkingof the tumor on the right pelvic sidewall, and left pel-vic lymph node debulking, and was staged as a FIGOIIIC. She subsequently underwent two cycles of che-motherapy with Taxol and Carboplatinum and was ad-mitted after the second cycle with progressive pelvicdisease and bulky retroperitoneal adenopathy causingbilateral ureteral obstruction, contributing to a rightvenous leg thrombosis, and resulting in vena cavalcompression syndrome. Bilateral ureteral stents wereplaced and palliative radiation was given to the venacava. She continued to do poorly and was dischargedto hospice care 4 months after the initial surgery. Sheexpired a few days later.

Pathology

The right adnexum was replaced by multiple tumornodules ranging in size from 8.5 � 5.5 � 3.5 cm to7.5 � 5.5 � 3.0 cm. The left adnexum was similarin appearance. Cut sections of the tumor revealeda mixed cystic and solid neoplasm with areas of ne-crosis. The cysts were filled with mucinous material.The tumor also involved the uterine serosa and omen-tum, as well as two right pelvic lymph nodes. Histo-logically, the majority of the tumor was composedof solid sheets of markedly atypical cells with abun-dant mitotic activity, consistent with anaplastic carci-noma (Fig. 1). Other areas were consistent with a highgrade mucinous cystadenocarcinoma (Fig. 2). The mu-cinous portion of the neoplasm stained diffusely withCK 7 and focally for CK 20, consistent with an ovar-ian primary, and the anaplastic portion was CK 7 pos-itive, CK 20 negative. The anaplastic tumor stainedfor vimentin, EMA, PLAP, and CK19, and was nega-tive for AFP, c-kit, inhibin, hCG, HPL, chromogranin,CD30, and HMB45. Cytogenetics showed multipleaberrations of the chromosomes, with a karyotypeof 62-75, X, Del(X)(q21), multiple aberrations [6]/46,XX[14].1

Discussion

Epithelial ovarian neoplasms are uncommon in ado-lescents. Most ovarian masses in this age group arenonneoplastic functional ovarian cysts.2 The most

Fig. 1. The majority of the tumor was composed of solid sheets of markedly atypical cells showing nuclear pleomorphism,with margination of the chromatin and prominent nucleoli. Mitotic activity was abundant.

41Vella et al: Anaplastic Carcinoma of the Ovary

Fig. 2. Areas of the tumor showed high grade mucinous cystadenocarcinoma.

common ovarian neoplasms in this age group aregerm cell tumors, of which most are benign cystic ter-atomas. In a review of 51 ovarian masses in adoles-cent girls,3 43% of the masses were functionalcysts. Of 29 neoplasms, 86% were germ cell tumors,of which 90% were benign teratomas, the rest beingmalignant germ cell tumors. Only 1 case (3%) wasa benign epithelial neoplasm. The most common pre-senting symptom was abdominal pain, often clinicallyinterpreted as appendicitis. This is in distinction to thepresentation in the older patient, where severe pain isan uncommon presenting symptom of ovarian malig-nancy. The most common misdiagnosis in the adoles-cent age group was appendicitis.

Foci of anaplastic carcinomas in ovarian mucinousneoplasms may be admixed with the carcinoma, as inour case, where there were histologic discrete foci, butno gross delineation of the two histologies, or theymay present as discrete mural nodules in a cysticovarian neoplasm. The differential diagnosis of muralnodules within mucinous cystic tumors of the ovary,although not broad, does create a diagnostic chal-lenge, and includes anaplastic carcinoma, sarcoma,sarcoma-like nodules, and the exceptionally rare car-cinosarcoma. Only a few case reports exist of muralnodules of carcinosarcoma. Chang et al4 report ona case arising in a borderline tumor, with a benignfollow-up of 19 months after surgery.

The fact that benign and malignant processes sharevery similar microscopic characteristics is compli-cated by the fact that both may contain a large numberof reactive histiocytic type cells.5 The issue is furthercomplicated because some reactive type lesions have

been described as undergoing pseudosarcomatous6

changes and may histologically mimic sarcoma.Bague et al7 reviewed ten cases of sarcoma-like nod-ules and postulate that they are a reactive phenome-non. Staining for both keratin and vimentin in theircases was consistent with an origin from submesothe-lial mesenchymal cells. The presence of these sarcoma-like nodules does not have an adverse impact on theprognosis of a case.

Cases of anaplastic carcinoma within a mucinousneoplasm can be differentiated from benign and reac-tive processes via careful examination. Reactive sarco-ma-like nodules, possibly resulting from hemorrhagewithin the cyst wall,8 may look very similar to anaplas-tic carcinoma on gross examination. Both tend to lookwell demarcated grossly, but only anaplastic carcinomahas been shown to invade microscopically, demonstrat-ing poor circumscription with stromal and vascular in-vasion.9 It has also been reported that nodules ofanaplastic carcinoma are firmer and less hemorrhagicthan sarcoma-like nodules.1 At the time of surgery, sar-coma-like nodules will be confined to the ovary, where-as anaplastic carcinomas may have already spreadbeyond the pelvis. Anaplastic carcinoma has also beenshown to be more homogeneous in population than sar-coma-like lesions, with the former containing cells withbizarre hyperchromatic nuclei and abundant eosino-philic cytoplasm.6 Anaplastic carcinoma will also dem-onstrate occasional gland formation,10 sometimes evenwith gland forming metastases.11 One should be care-ful, however, not to mistake entrapment of normalglands within a tumor as gland formation by the tu-mor.12 Some difficulties in differential diagnosis have

42 Vella et al: Anaplastic Carcinoma of the Ovary

been alleviated by tumors containing both sarcoma-likemural nodules, and foci of anaplastic carcinoma,12

allowing direct comparison.Some studies report the use of electron microscopy

to demonstrate epithelial differentiation within muralnodules. Ultrastructural findings, such as intercellularand intracellular lumina, microvilli, and intercellularjunctional complexes, have been used to confirm thecarcinomatous origin of such lesions.8,10,13,14

All reported cases of anaplastic carcinoma inwhich immunohistochemistry has been performedhave shown positivity for cytokeratin,6,8,11,14,15 withsome cells containing intracytoplasmic mucin.8 Mat-ias-Guiu et al6 state that although sarcoma-like muralnodules may contain a few keratin positive cells,a strong diffuse positivity for keratin should be inter-preted as anaplastic carcinoma. Results of CEA stain-ing have been equivocal8,13 and vimentin has beenshown to be negative in some nodules,8,13,15 whileweakly positive in others.8,11,13–16

Little has been written about distinguishing ana-plastic carcinoma from true sarcoma, possibly be-cause the distinction has little if any prognosticsignificance.1 Careful histological examination andimmunohistochemical technique, however, can proveuseful in making such distinctions. It should be notedthat while extraovarian spread in a mucinous carcino-ma with an anaplastic carcinomatous component isassociated with an aggressive course, this is not truefor early stage disease. Rodriguez et al identified 19cases of mucinous carcinomas with foci of anaplasticcarcinoma. Five of these cases were stage IA, and inthese cases, the presence of anaplastic carcinoma didnot have an adverse effect on outcome. Prognosticfeatures in this series of mucinous ovarian neoplasmsincluded infiltrative stromal invasion for early stagetumors, and FIGO stage, with nuclear grade and tumorrupture somewhat less prognostically important.17

The pathogenesis of anaplastic carcinomas arisingwithin mucinous tumors of the ovary is not clear.Czernobilsky et al18 believe that they are the resultof a progressive dedifferentiation of mucinous carci-noma cells with subsequent loss of mucin production.This was based on the observation of a focus of mu-cinous carcinoma merging with anaplastic elements.Similar features were reported by Chen et al9 andNichols et al.11 To date, less than 30 cases of fociof anaplastic carcinoma within a mucinous carcinomahave been reported, and incidence in an adolescent isexceptional.8,10–13,15,16,18–21 This case illustrates that,although rare, persistent abdominal pain in an adoles-cent female may represent an ovarian epithelial ma-lignancy. The question arises as to whether tosubject every adolescent with abdominal pain to a pel-vic examination and/or ultrasound. Given the rarity ofovarian malignancy in this age group, and the

frequency of the vague symptom of abdominal pain,this does not seem indicated in all cases. However,keeping the possibility of a rare malignancy in mindmay lead to further investigations in cases of persis-tent unexplained pain.

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