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Breast Cancer

Vol. 12 No. 2 April 2005

Case Report

Invasive cribriform carcinoma (ICC) is a uniquetype of invasive breast carcinoma that was firstdescribed by Page et al. in 1983; the carcinoma ischaracterized by a cribriform pattern in the major-ity of its invasive component1). Cases have beendivided into pure, classical, and mixed forms ofICC2, 3). In the pure form, most of the invasive com-ponent exhibits a cribriform pattern2-4). In the clas-sical and mixed forms, less than 50% of the tumorconsists of other histological types of invasive car-cinoma1-3). The prognosis of patients with pure

and classical ICC is excellent1-5). The incidence ofmixed or pure ICC is 0.8% to 3.5% of all invasivebreast carcinomas1-4), and only one male patientwith ICC has been previously reported4). AlthoughICC has been suggested to contain a small num-ber of microcalcifications based on mammogra-phy studies6), only 1 previous case with histologi-cal evidence of extensive micrcalcification fromICC has been reported7).

Herein, a second male patient with ICC, whoexhibited extensive microcalcifications, is report-ed.

Case History

A tumor in the left breast of a 64-year-old Japan-ese man was discovered by computed tomogra-phy during an annual check up. The patient hadno complaints of nipple discharge or pain. Onphysical examination, an ill-defined hard nodule

Departments of ＊1Clinical Laboratory and ＊2Surgery, National Hospital Organization Shikoku Cancer Center, Japan;and ＊3Department of Surgery, Kochi Municipal Hospital, Japan.

Rieko Nishimura＊1, Shozo Ohsumi＊2, Norihiro Teramoto＊1, Takashi Yamakawa＊3, Toshiaki Saeki＊2,and Shigemitsu Takashima＊2

Key words: Breast, Male, Invasive cribriform carcinoma, Microcalcification

Invasive cribriform carcinoma (ICC) is a rare, unique type of invasive breast carcinoma that exhibits acribriform pattern in the majority of the invasive component and is associated with an excellent prognosis.Only one male patient with ICC has been previously reported. Mammography studies often suggest thatICC contains microcalcifications, but the histological finding of extensive microcalcification has only beenreported in one patient with ICC. Here we report a male patient diagnosed with ICC and exhibiting histo-logically confirmed extensive microcalcification is reported. The patient was a 64-year-old Japanese manin whom a breast tumor was detected during an annual check up. Mammography demonstrated a circum-scribed high-density mass with microcalcifications. Breast-conserving surgery with axillary node dissec-tion was performed. The tumor was located in the subareolar region of his left breast. The excised tumorhad a maximum diameter of 1.0 cm, and no signs of invasion to extramammary tissue were observed. His-tologically, the tumor cells were arranged in a cribriform pattern with invasive and non-invasive compo-nents. High-grade carcinoma or tubular carcinoma components were not observed. Extensive calcificationwas seen within the cribriform spaces. Immunohistological staining revealed that the cribriform spacesdid not contain basement membrane material, and the tumor cells had not differentiated into basaloidcells or lactationl mammary epithelium. The patient is presently free from local recurrence or metastasis 7months after undergoing surgery.

Breast Cancer 12:145-148, 2005.

Reprint requests to Rieko Nishimura, Department of ClinicalLaboratory, National Hospital Organization Shikoku CancerCenter, Horinouchi 13, Matsuyama, Ehime 790-0007, Japan.E-mail: rnishimu@shikoku-cc.go.jp

Abbreviations:ICC, Invasive cribriform carcinoma; ACC, Adenoid cysticcarcinoma; SC, Secretory carcinoma; H-E, Hematoxylin andeosin; PAS, Periodic acid-Schiff

Received June 1, 2004; accepted December 4, 2004

Invasive Cribriform Carcinoma with Extensive Microcalcifications inthe Male Breast

measuring 1.6×1.3 cm was found in the subareo-lar region of his left breast. The nodule wasmobile, with no adhesions to the skin or fascia. Amammography study demonstrated a circum-scribed high-density mass with microcalcification,and malignancy was suspected (Fig 1). Ultra-sonography revealed a borderline lesion. Fineneedle aspiration cytology showed malignantcells. Serum tumor markers and other routineblood test results were normal. A computedtomography evaluation was negative for metastat-ic disease. Thus, a breast-conserving surgery withskin and nipple excision and left axillary node dis-section was performed. The patient is presentlyfree from local recurrence and metastasis 7months after undergoing surgery.

Pathological Findings

The excised breast tumor had a maximumdiameter of 1.0 cm, and no signs of invasion toextramammary tissue were seen. The cut surfaceof the tumor showed a well-circumscribed, hard,grayish-brown tumor.

Microscopically, the tumor consisted of a well-demarcated round nodule with focal invasion toadipose tissue in the breast (Fig 2A). The tumorcells were arranged in a cribriform pattern in boththe invasive and non-invasive components (Fig2B). The non-invasive component composed lessthan 5% of the entire tumor. High-grade carcino-ma or tubular carcinoma components were notobserved. The nuclei of the tumor cells were rela-tively small, and the nucleoli were inconspicuous.

Mitotic figures were sparse (Fig 2C). Stainingwith von Kossa stain revealed extensive calcifica-tion in the cribriform spaces (Fig 2D).

The cribriform spaces did not stain with peri-odic acid-Schiff (PAS) or alcian blue, but diastase-digested PAS-positive granules were observed inthe cytoplasm of the tumor cells. Therefore, thecribriform spaces were considered to not containbasement membrane material or mucin, and thetumor cells were considered to contain glycogenin their cytoplasm.

Immunohistochemical staining was performedusing formalin-fixed, paraffin-embedded tissuesections. The cytoplasm of the tumor cells wasfocally positive for carcinoembryonic antigen,S100 protein, and gross cystic disease fluid pro-tein 15, but totally negative for vimentin, high mol-ecular weight keratin (CK34βE12), cytokeratin19, and muscle actin. Nuclear positivity was seenagainst antibodies to estrogen receptors and prog-esterone receptors. Therefore, the cribriformspaces were considered to not contain basementmembrane material, and tumor cell differentiationinto basaloid cells or lactationl mammary epitheli-um was considered to be absent.

Discussion

ICC is a unique type of invasive breast carcino-ma that was first described by Page et al. in 19831).The histological hallmark of ICC is a cribriformpattern in the majority of the invasive compo-nent2, 3). Page et al. used the term ICC to describebreast carcinoma that exhibits a cribriform pat-tern in more than 50% of the invasive componentand divided the condition into classical ICC andmixed ICC1). Classical ICC consists of a tumor thatexhibits an exclusively cribriform pattern or crib-riform pattern with a limited extent of tubularinvasive elements only, while mixed ICC containsareas of less well-differentiated invasive carcino-ma1). Some authors use the term “pure ICC” todescribe tumors that do not exhibit any otherforms of invasive carcinoma2-5). The prognosis ofpure and classical ICC is excellent1-5). The inci-dence of mixed or pure ICC is 0.8 to 3.5% of allinvasive breast carcinomas1-4), and only one malepatient has been previously reported4). It is stillcontroversial whether ICC is a special histologicaltype or one of the pattern of ordinary invasiveductal carcinoma1). ICC may be classified intopapillotubular carcinoma accoding to the General

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Fig 1．Mammography findings show a circumscribed high-density mass with microcalcifications.

rules for clinical and pathological recording ofbreast cancer edited by the Japanese Breast Can-cer Society8).

ICC must be distinguished from other invasivebreast carcinomas that exhibit a cribriform pat-tern, like adenoid cystic carcinoma (ACC) andsecretory carcinoma (SC)1-4, 9). ACC may exhibit acribriform pattern in some areas. However, thecribriform spaces in ACC lesions contain base-ment membrane material, whereas the cribriformspaces in ICC lesions do not8). ACC also containsbasaloid cells (myoepithelium-like cells), in addi-tion to glandular cells2, 3). SC is an invasive breastcarcinoma that resembles lactational mammaryglands and presents with extensive secretion. Fur-thermore, SC is positive forα-lactoalbumin in thecytoplasm of the tumor cells2, 3). ICC, on the other

hand, does not exhibit extensive secretion and isnegative forα-lactoalbumin3). Therefore, the pre-sent case was diagnosed as ICC.

Histologically confirmed extensive microcalci-fication in ICC has only been reported in one pre-vious case7), though ICC has been suggested tocontain microcalcifications on the bases of mam-mography findings6). Shousha et al. reported acase of extensive microcalcifications in a womanwith ICC who had a 20-year history of siliconeaugmentation7). They explained that the calcifica-tions in their case were the result of an activesecretory process by the tumor cells, based onelectron micrography studies, but the relationbetween the calcification and silicon, if any, wasunclear. The man described in the present reportdid not have a history of silicone augmentation,

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Fig 2．Microscopic appearance of the breast tumor. (A) Panoramic view of the tumor shows a well-demarcated round nodulewith focal invasion to the breast’s adipose tissue. (B) The tumor cells are arranged in cribriform patterns in the invasive (right)and non-invasive (left) components. High grade carcinoma or tubular carcinoma components are not visible (H-E stain,×4, objec-tive). (C) Calcification is visible within the cribriform spaces. The nuclei of the tumor cells are relatively small, and the nucleoli areinconspicuous. Mitotic figures are sparse (H-E stain,×40, objective). (D) Extensive calcification is visible in the cribriform spaces(von Kossa stain,×20, objective).

suggesting that the microcalcifications observedin the cribriform spaces of the tumor may be atypical appearance of this histology, arising fromactive secretion by the tumor cells themselves.Microcalcifications in ICC are also unique for aninvasive carcinoma, because extensive microcalci-fications mainly occur in the non-invasive compo-nents of breast carcinoma10).

Acknowledgements

We thank Drs. Goi Sakamoto and Futoshi Akiyama ofJapanese Foundation for Cancer Research, and Dr.Takahiro Hasebe of National Cancer Center ResearchInstitute East for their advice regarding the diagnosis ofthis case and Dr. Rie Horii of Japanese Foundation forCancer Research for advice on the immunohistochemicalstaining. We also thank Ms. Tamami Yamamoto, Ms.Emi Nakaya, and Ms. Sachiko Morita of our institute fortheir skillful immunohistochemical staining techniques.

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of Tumours) IARC Press, International Agency forResearch on Cancer, Lyon, pp9-112, 2003.

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4) Venable JG, Schwartz AM, Silverberg SG: Infiltratingcribriform carcinoma of the breast: a distinctive clini-copathologic entity. Hum Pathol 21:333-338, 1990.

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7) Shousha S, Schoenfeld A, Moss J, Shore I, SinnettHD: Light and electron microscopic study of an inva-sive cribriform carcinoma with extensive microcalcifi-cation developing in a breast with silicone augmenta-tion. Ultrastruct Pathol 18:519-523, 1994.

8) Japanese Breast Cancer Society: General rules forclinical and pathological recording of breast cancer.15th Ed, Kanehara Shuppan, Tokyo, 2004 (in Japan-ese).

9) Wells CA, Ferguson DJP: Ultrastructural and immuno-cytochemical study of a case of invasive cribriformbreast carcinoma. J Clin Pathol 41:17-20, 1988.

10) Rosen PP: Pathology of mammary calcifications. In:Rosen’s breast pathology. 2nd Ed, LippincottWilliams & Wilkins, Philadelphia, pp943-947, 2001.

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