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Breast cancer may express the presence of b-human chorionic gonadotrophin in 12%1 to 18% of cases,2 using immunohisto-chemical reactions. Usually the tumors will show positivity in a few scattered cells. Of women with breast cancer, 12 to 13% show elevated levels of serum human chorionic go-nadotrophin.2 Breast cancer with choriocar-cinomatous features, as reported by Saigo and Rosen,2 is a distinct variant of breast cancer. Histologically, such tumors show pleomor-phic areas of large-sized, oval-shaped tumor cells with a high nuclear-to-cytoplasmic ra-tio and increased nuclear chromatin. T he cy-toplasm of the tumor cells is pale to eosi-nophilic with occasional periodic acid-Schiff stain-positive intracytoplasmic eosinophilic globules. O ccasional multinucleated giant cells are also seen. T hese findings are similar to choriocarcinoma originating from the genital tract.3 We report a case of breast can-cer with choriocarcinomatous and neuroen-docrine features.
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Clinical Course
T he patient was a 50-year-old Brazilian woman who reported a mammary lump with progressive growth in the upper outer quad-rant of the right breast. It was first noticed about 3 months before she underwent quadrantectomy. T he specimen revealed a 7 x 6.5 x 4.5 cm tumor with infiltrative borders and areas of necrosis and hemorrhage of the cut surface. Histology of the lesion showed the presence of an invasive ductal carcinoma
with areas of giant cells and intense atypia. Following confirmation of a malignant breast tumor, a right mastectomy with ipsi-lateral axillary lymph node dissection was per-formed. During the operation, no distant metastasis was observed in any organ. Meas-urements of serum human chorionic gonado-trophin and female sex hormones were not performed in the preoperative period.
Pathologic findings
T he specimen showed an ill-defined tumor, 7 x 6.5 x 4.5 cm in size, located in the upper outer quadrant of the right breast with infiltrative borders. T he cut surface showed areas of necrosis and hemorrhage.
Histologically, the tumor revealed an in-vasive ductal carcinoma with pleomorphic areas that showed multinucleated giant cells and intense atypia and areas with less pleo-morphism (Figure 1).
Vascular permeation of tumor cells was inconspicuous. T he product from the right mastectomy showed no residual neoplasia. T here was also no angiovascular, skin or nip-ple infiltration. All of the 20 axillary lymph nodes dissected were free from metastasis.
Immunohistochemical findings
T he tissue for immunohistochemical in-vestigation was embedded in paraffin after be-ing fixed in 10% formalin solution. T he speci-mens were stained with chromogranin, synaptophysin, human chorionic gonado-trophin and cytokeratin (AE-1/AE-3) using the avidin-biotin peroxidase complex method with hematoxylin counterstaining.
T he reaction was positive in the pleo-morphic areas for human chorionic
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• O svaldo G iannotti Filho
• Luciana N akao O dashiro M iiji
• M arta Vainchenker
• Ângela N avarro G ordan
Breast cancer with
choriocarcinomatous and
neuroendocrine features
Department of Pathology, Universidade Federal de São Paulo/Escola
Paulista de Medicina, São Paulo, Brazil
CO N TEX T: Bre a st c a nc e r ma y e xpre ss the pre se nc e o f b -huma n c ho rio nic g o na do tro phin in 1 2 % to 1 8 % o f c a se s, using immuno histo c he mic a l rea c tio ns. Usua lly the tumo rs will sho w po sitivity in a fe w sc a tte re d c e lls. Bre a st c a nc e r w ith c ho rio c a rc ino ma to us fe a ture s, a s re po rte d b y Sa ig o a nd Ro se n, is a distinc t va ria nt o f b re a st c a nc e r. W e re po rt a c a se o f b re a st c a nc e r with c ho rio c a rc ino ma to us a nd ne uro e ndo c rine fe a -ture s.
OBJECTIVE: This is a case repo rt o f an invasive ductal carcino ma o f the breast with cho rio carcino mato us and neuro endo crine features.
DESIGN : Case Repo rt.
CASE REPORT: A 5 0 -year-o ld Brazilian wo man un-derwent surg ery fo r a lump in the rig ht breast, which had been first no ticed abo ut 3 mo nths earlier. The surg ery co nsisted o f quadrantecto my fo llo wed b y rig ht ma stec to my with ipsila tera l axillary lymph no de dissectio n. The specimen fro m the quadrantecto my revealed a 7 x 6 .5 x 4 .5 cm tumo r. Histo lo g y o f the lesio n sho wed the presence o f an invasive ductal carcino ma with areas o f g iant cells and intense atypia. The im-muno histo chemistry was po sitive in the pleo mo r-phic areas fo r human cho rio nic g o nado tro phin, while the less pleo mo rphic areas sho wed po sitivity fo r synapto physin and chro mo g ranin.
KEY W ORDS: Breast cancer. Cho rio carcino mato us features. Cho rio carcino mato us and neuro endo -crine features.
São Paulo M edical Journal - Revista Paulista de M edicina
155
dotrophin (Figure 2), while the areas with less pleomorphism showed focal positivity for synaptophysin and chromogranin. T he cytokeratin (AE-1/AE-3) was positive as ex-pected and the other immunohistochemi-cal findings were foimmunohistochemi-cal positivity for estrogen receptor and negativity for progesterone receptor.
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Some mammary carcinomas are able to synthesize hormones not considered to be nor-mal products of the breast. Such tumors have been found to produce peptide hormones in-cluding human chorionic gonadotrophin, cal-citonin and epinephrine. Breast cancer may express the presence of b-human chorionic go-nadotrophin in 12%1 to 18%2 of the cases, using immunohistochemical reactions. Usu-ally the tumors will show positivity in a few scattered cells. In our case, b-human chori-onic gonadotrophin was focally positive. An-other unexpected finding was the positive re-activity in the less pleomorphic areas to both chromogranin and synaptophysin, showing neuroendocrine differentiation in addition to the choriocarcinomatous features.
Neoplasms with neuroendocrine differen-tiation do not constitute a specific histopatho-logical category of female mammary carci-noma, but it is apparent that there is a group of mammary carcinomas capable of produc-ing ectopic hormonal substances. T he recog-nition of these features is necessary for defin-ing their clinical characteristics. Moreover, some studies show that nearly half of the
pa-tients had axillary nodal metastasis and also a higher frequency of recurrence and death due to breast carcinoma. However, there have been no case-controlled studies of pa-tients who have mammary carcinoma with neuroendocrine differentiation with age, which compare these with stage-matched control groups. T hus, neither ectopic hor-mone production nor endocrine differen-tiation has proven to be a factor that criti-cally influences prognosis or treatment.
O n the other hand, the choriocar-cinomatous features of this case allow it to be classified as the distinct variant of breast cancer reported by Saigo and Rosen.2 It is a unique variant of ductal car-cinoma with focal choriocarcar-cinomatous components. T he choriocarcinomatous component is usually associated with con-ventional infiltrating ductal carcinoma such as solid tubular carcinoma.3 Mucoid carcinoma of the breast with chorio-carcinomatous components in the meta-plastic area has also been reported.1 T he cellular origin of breast cancer with choriocarcinomatous features is uncertain. Nevertheless, conventional ductal carcino-mas in breast cells may sometimes show positive immunohistochemical reactivity for human chorionic gonadotrophin.3
Finally, the importance of diagnosing the choriocarcinomatous features in an in-vasive ductal carcinoma is that such tumors are highly malignant. T heir clinical course is usually aggressive and most patients die within a few months due to multiple metastases.
Figure 2. Immunohistochemistry: large and bizarre tumor cells showing positivity for chorionic gonadotrophin (X400).
Figure 1. Pleomorphic area with large-sized, atypical tumor cells, multinucleated giant cells and atypical mitosis (HE, X100).
CONTEXTO: O câncer de mama pode expressar a presença da gonadotrofina coriônica humana-beta (b-HCG) em 12% a 18%, por reações imunohistoquímicas. Usualmente, apenas algumas células do tumor mostrarão positividade. Câncer de mama com carac-terísticas coriocarcinomatosas, descrito por Saigon e Rosen, é uma variante distinta do câncer de mama. Descrevemos um caso de câncer de mama com padrões coriocarci-nomatosos e neuroendócrinos.
OBJET IVO: Esse é um relato de caso de um carcinoma ductal invasivo de mama com características coriocarcinomatosas e neuroendócrinas.
TIPO DE ESTUDO: Relato de caso.
RELATO DE CASO: Mulher de 50 anos de idade, brasileira, apresentou um nódulo na
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mama direita que foi notado primeiramente três meses antes da cirurgia, fez uma quadrantectomia seguido de uma mastec-tomia direita com linfadenecmastec-tomia ipsilateral. A peça cirúrgica da quadrantectomia mostrou um tumor de 7 x 6, 5 x 4, 5 cm. A histologia da lesão revelou um carcinoma ductal invasivo com áreas de células gigantes e intensas atipias. O estudo imunohistoquímico revelou positividade nas áreas pleomórficas para gonadotrofina coriônica humana (b-HCG), enquanto que as áreas de menor pleo-morfismo mostraram positividade para sinaptofisina e cromogranina.
PALAVRAS-CHAVE: Câncer de mama. Câncer com características coriocarcinomatosas. C âncer de mama com características coriocarcinomatosas e neuroendócrinas.
Osva ldo Gia nnotti Filho, M D, PhD. Adjunct Pro fesso r, Department o f Patho lo g y, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Braz il.
Lucia na N a k a o Oda shiro M iiji, M D. Medical Resident, Department o f Patho lo g y, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Braz il.
M a rta Va inchenk er, M D. Medical Resident, Department o f Patho lo g y, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Braz il.
Ângela N a va rro Gorda n, M D. Medical Resident, De-partment o f Patho lo g y, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Braz il.
Sources of funding: N o ne
Conflict of interest: N o ne
La st received: 1 8 / 0 1 / 2 0 0 1
Accepted: 1 3 / 0 3 / 2 0 0 1
Address for correspondence
O svaldo G ianno tti Filho
Departamento de Pato lo g ia da Esco la Paulista de Medicina - Universidade Federal de São Paulo R. Botucatu, 740 - São Paulo/ SP - Brazil - CEP 04023-900 E-mail: g ianno tti@ pato lo g ia.epm.br
CO PYRIG HT© 2 0 0 1 , Asso ciação Paulista de Medicina
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1. Green DM. Mucoid carcinoma of the breast with choriocarcinoma in its metastasis. Histopathology 1990;16:504-6.
2. Saigo PE, Rosen PP. Mammary carcinoma with “choriocarcinomatous” features. Am J Surg Pathol 1981;5:773-8.
3. Murata T, Ihara S. Breast cancer with choriocarcinomatous features: a case report with cytopathological details. Pathol International 1999;49:816-9.
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