A case of pure cribriform carcinoma of the breast, as-
sociated with an intraductal cribriform component and
metastatic involvement of an internal mammary lymph
node, observed at the European Institute of Oncology in
Milan is reported. The pathological and clinical charac-
teristics are discussed.
A 58-year-old postmenopausal woman was admitted
to the Division of Breast Surgery of our Institute with a
left breast lesion highly suspicious for malignancy. The
family history of the patient revealed no cases of breast
carcinoma among relatives; she had no personal history
of other neoplasms and had not previously been ex-
posed to radiotherapy. The patient suffered from osteo-
porosis and was treated with aledronate (70 mg/week).
She had undergone a hysterectomy when she was 40
years old and had been exposed to HRT for at least 10
years (she stopped HRT at the moment of breast cancer
Physical examination revealed a mobile irregular
mass of 1 cm in largest clinical diameter in the lower
internal quadrant of the left breast. The disease did not
involve the skin and there was no nipple discharge.
In the presurgical diagnostic workup the patient un-
derwent a bilateral mammogram which showed a dense
area in the breast parenchyma, highly suspicious for
malignancy. Breast ultrasound showed a 1.1 cm, irregu-
larly shaped hypoechogenic mass. Fine-needle aspira-
tion cytology was performed, with a report of hematic
material including fibrous fragments (C-1).
On the basis of the diagnostic evaluation and clinical
suspicion of breast carcinoma, the patient underwent an
inner quadrantectomy with sentinel node biopsy in the
axilla and internal mammary node biopsy. Intraopera-
tive pathological examination confirmed the presence
of invasive carcinoma. Intraoperative radiotherapy with
electrons (ELIOT) was performed at a dose of 21 Gy.
Final histology showed a pure cribriform carcinoma,
grade I, associated with an intraductal cribriform com-
ponent. The maximum diameter of the tumor was 1.2
cm. The 2 sentinel nodes sampled in the axilla were
negative for metastasis and no axillary dissection was
performed. The internal mammary node was metastatic.
The surgical specimen contained a greyish tumor
with ill-defined margins with a diameter of 1.2 cm. His-
tological examination showed an almost pure (>90%)
cribriform pattern of growth with mild nuclear pleomor-
phism and a low mitotic index. The tumor was classi-
fied as pure cribriform carcinoma and graded as G1. An
intraductal cribriform component, representing less than
10% of the tumor, was associated with the invasive tu-
mor. The surgical resection margins were free of tumor.
Immunohistochemical analysis showed strong nu-
clear immunoreactivity for estrogen receptors in more
than 95% of the tumor cells, while progesterone recep-
Tumori, 92: 241-243, 2006
REPORT ON ACASE OF PURE CRIBRIFORM CARCINOMAOF THE BREAST
WITH INTERNAL MAMMARY NODE METASTASIS:
DESCRIPTION OF THE CASE AND REVIEW OF THE LITERATURE
Giovanna Gatti1,2, Giancarlo Pruneri3,4, Daniela Gilardi1, Fabricio Brenelli1, Guillermo Bassani1,
and Alberto Luini1,4
1Division of Breast Surgery, European Institute of Oncology, Milan; 2Postgraduate School of General Surgery, University of Perugia, Perugia;
3Division of Pathology, European Institute of Oncology, Milan; 4University of Milan School of Medicine, Milan, Italy
Key words: cribriform carcinoma of the breast, internal mammary node metastases, lymph node metastases.
Aims and background: Pure ductal invasive carcinoma of the
breast is more frequently associated with lymphatic invasion,
lymph node involvement and high malignant histological
grade than combined forms of breast carcinoma. Internal
mammary node metastases are not frequently detected when
the axillary nodes are negative.
Patients and methods: We report our experience of a case of
pure cribriform carcinoma, associated with an intraductal
cribriform component, in which the sentinel axillary nodes
were negative, while nodal and perinodal metastasis was de-
tected in one internal mammary lymph node.
Conclusions: Data from the literature show that positive in-
ternal mammary nodes are an unusual finding when the ax-
illary sentinel node is negative, especially in cases of can-
cer with a relatively good prognosis, such as cribriform
Correspondence to: Giovanna Gatti, MD, Division of Breast Surgery, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
Tel +39-02-57489215; fax +39-02-57489210; e-mail firstname.lastname@example.org
Received August 8, 2005; accepted January 26, 2006.
G GATTI, G PRUNERI, D GILARDI ETAL
1. Viale G, Bosari S, Mazzarol G, Galimberti V, Luini A,
Veronesi P, Paganelli G, Bedoni M, Orvieto E: Intraoperative
examination of axillary sentinel lymph nodes in breast carci-
noma patients. Cancer, 85: 2433-2438, 1999.
2. Bonadonna G, Valagussa P: Neoplasie della mammella. In:
Medicina Oncologica, Bonadonna G, Robustelli della Cuna
G (Eds), pp 615-656, Masson, Milano, 1994.
3. Rilke F, Di Palma S: Istopatologia delle lesioni maligne. In:
tors and HER2/neu expression were lacking. As expect-
ed, the Ki67 labeling index was very low (3%).
Two axillary sentinel lymph nodes, examined intra-
operatively as previously reported1, showed no metasta-
tic involvement. By contrast, formalin-fixed and paraf-
fin-embedded sections of an internal mammary lymph
node measuring 0.3 cm in diameter showed nodal and
perinodal metastasis of cribriform carcinoma. In accor-
dance with the recommendations of the Sixth Edition of
the UICC TNM classification, the tumor was staged as
Cribriform invasive carcinoma represents one of the
special histological types of invasive breast cancer, to-
gether with medullary, tubular, mucinous and lobular
types. These histological types represent about 20-30%
of mammary tumors. With the exception of medullary
carcinomas, pure forms of the special histological types
are characterized by a good prognosis: they are almost
always free of distant metastases.
Pure ductal invasive carcinoma is more often associ-
ated with lymphatic invasion, palpable adenopathy and
high histological grade than are combined forms; in
particular, pure ductal carcinomas show a more malig-
nant clinical and biological behavior than combined
forms in which a special histological type is detected
(again with the exception of medullary forms).
Pure cribriform carcinoma is quite rare; it is more fre-
quently associated with tubular carcinoma, both of
which are characterized by a good prognosis. Paradoxi-
cally, when associated with ductal invasive carcinoma,
the prognosis becomes worse in proportion to the exten-
sion of the invasive cribriform component1-3.
Internal mammary node (IMN) involvement varies in
the published data. Veronesi et al. found IMN involve-
ment in approximately 20.5% of women who had un-
dergone extended mastectomy with internal mammary
node dissection. In 16% of cases IMN involvement was
associated with axillary metastasis, while in 4% there
was no axillary disease. The authors concluded that the
involvement of IMNs seems to have prognostic value in
axillary node-negative and positive patients4.
Galimberti et al. published the results of a study con-
ducted at the European Institute of Oncology between
September 1998 and September 20015. The study popu-
lation consisted of breast cancer patients who were can-
didates for sentinel node biopsy by radiotracer, in whom
radioactive uptake to the IMN region was evident on
the lymphoscintigram. At pathological examination, on-
ly 14 (8.8%) of the examined patients had metastatic
IMNs. In four cases (2.5%) there was a metastatic IMN
without axillary involvement. Four other patients had
micrometastasis in the IMNs.
Dupont et al. found that 2.4% of patients who under-
went lymphatic mapping for breast cancer had at least
one IMN removed; 73% had inner quadrant lesions. Only
in 16.7% of patients with IMNs removed was there
metastatic disease in the IMNs, and 10% of the study
population only had metastasis to the IMN basin. Further-
more, 4 of the 5 patients with metastases to the IMN
basin had lobular or mixed lobular and ductal carcinoma6.
Veronesi et al. found that metastases to the internal
mammary chain were significantly associated with pa-
tient age and maximum diameter of the primary tumor.
Patients with positive axillary nodes had metastases to
IMNs in 29.1% of cases, while 9.1% of patients with
metastatic IMNs had no axillary involvement. The au-
thors also noted that the frequency of metastases to an
IMN is slightly increased when the primary tumor is lo-
cated in the central quadrant of the breast (22%), com-
pared to inner (19.1%) and external lesions (18%)7.
Cody et al. found that 18% of 195 patients who un-
derwent an extended mastectomy had internal mamma-
ry metastases but no axillary involvement8.
The case of a patient with metastatic IMN and nega-
tive axillary nodes was reported by Julián et al. The pa-
tient was affected by invasive ductal carcinoma, grade
II/III, diameter 2.2 cm. There were several foci of
comedo, cribrifom, and solid carcinoma in situ span-
ning 25% of the tumor mass. The sentinel node from
the second intercostal space displayed several mi-
crometastatic foci (<2 mm) in the capsular sinus9.
The metastatic status of the IMNs is as important as
the status of the axillary nodes for prognosis; moreover,
the prognosis is very unfavorable if both axillary nodes
and IMNs are involved. Patients with either axillary or
IMN metastasis have an intermediate prognosis7,9-11.
In conclusion, data from the literature show that
metastases to the IMNs in the absence of axillary in-
volvement can be found in different percentages of cas-
es in various study populations. Data from the European
Institute of Oncology show that 2.5% of patients who
are IMN positive are negative in the axilla5.
In the case described here, the patient had a poorly
aggressive cancer, characterized by a relatively small
diameter, no peritumoral vascular invasion and a histo-
logical type usually associated with a good prognosis.
This tumor was associated with macroscopic metastasis
to the IMN and a pathologically negative axilla. The de-
finitive pathology justified the collegial decision to of-
fer this patient chemotherapy with anthracyclines and
locoregional radiotherapy to the internal mammary
chain, despite the histopathological nature of the tumor
and the absence of axillary metastasis.
PURE CRIBRIFORM CARCINOMAOF THE BREAST WITH NODAL METASTASES Download full-text
Manuale di Senologia Oncologica, Veronesi U (Ed), pp 49-
67, Masson, Milano, 1994.
4. Veronesi U, Marubini E, Mariani L, Valagussa P, Zucali R:
The dissection of internal mammary nodes does not improve
the survival of breast cancer patients. 30-year results of a ran-
domised trial. Eur J Cancer, 35: 1320-1325, 1999.
5. Galimberti V, Veronesi P, Arnone P, De Cicco C, Renne G,
Intra M, Zurrida S, Sacchini V, Gennari R, Vento AR, Luini
A, Veronesi U: Stage migration after biopsy of internal mam-
mary chain lymph nodes in breast cancer patients. Ann Surg
Oncol, 9: 924-928, 2002.
6. Dupont E, Cox CE, Nguyen K, Salud CJ, Peltz ES, White-
head GF, Ebert MD, Ku NN, Reintgen DS: Utility of internal
mammary lymph node removal when noted by intraoperative
gamma probe detection. Ann Surg Oncol, 8: 833-836, 2001.
7. Veronesi U, Cascinelli N, Greco M, Bufalino R, Morabito A,
Galluzzo D, Conti R, De Lellis R, Delle Donne V, Piotti P:
Prognosis of breast cancer patients after mastectomy and dis-
section of internal mammary nodes. Ann Surg, 202: 702-707,
8. Cody H, Urban JA: Internal mammary node status: a major
prognosticator in axillary node-negative breast cancer. Ann
Sur Oncol, 2: 32-37, 1995.
9. Julián FJ, Fraile M, Llatjós M, Rull M, Fusté F, Castellà E,
Vallejos V, Mariscal A, Barnadas A, Alastrué A: Internal
mammary sentinel node metastases in an otherwise lymph-
node negative breast cancer patient. Breast J, 8: 317-319,
10. Noguchi M, Tsugawa K, Miwa K: Internal mammary chain
sentinel lymph node identification in breast cancer. J Surg
Oncol, 73: 75-80, 2000.
11. Lacour J, Le MG, Hill C, Kramar A, Contesso G, Sarrazin D:
Is it useful to remove internal mammary nodes in operable
breast cancer? Eur J Surg Oncol, 13: 309-314, 1987.