Sabato 27 ottobre 2012 - Pacini Editore

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MRI demonstrated pancreas with structural alterations at the
uncinate portion due to the presence of a nodular mass of around
3.5cm with a fluid component in itscontext. The formation appeared
with a vanishing profile and was strictly adherent to the
anterior wall of the third duodenal.
On the basis of above findings, the presence of a tumor in the
uncinate process of the pancreas was strongly suspected.
The patient was subjected to cefaloduodenopancreasectomy.
Macroscopic examination of the surgical specimen showed a
well-demarcated round yellowish mass measuring 4x3.5 cm.
Final histology demonstrated a ductal adenoncarcinoma of tha
pancreas (G3) with a signet ring cells component. The neoplasms
infiltrated the intestinal wall and peripancreatic tissue. None of the
13 peripancreatic lymph node has shown a center of metastases.
The patient was kept on regular follow-up by the oncologist for
palliative cure.
Gastric metastases from lobular breast carcinoma:
a diagnostic challenge
A. Guadagno * , T. Celiento * , F. Sarocchi * , M. Gualco ** , R. Ponte * ,
P. Calamaro * , F. Grillo * , L. Mastracci *
* ** University of Genoa, Histopathology DISC; IST S.C. of Anatomy,
Cyto-Histology and Pathology, Azienda Ospedaliera Universitaria San
Martino-IST- I.R.C.C.S. Largo Rosanna Benzi 10 Genoa, Italy
Introduction. A study, over a 30-year period from 1993, reports
more than 1000 cases of gastrointestinal metastases from breast
cancer 1 . The incidence of extrahepatic gastrointestinal tract
metastases from lobular carcinoma observed in autopsy studies
varies in the literature from 6% to 18% with the most commonly
affected organ being the stomach, small bowel followed by colon
and rectum 2 . Gastric metastases of breast carcinoma are rare
but when they occur they represent a major diagnostic dilemma
especially if incomplete clinical information is given. We report
two cases of metastatic breast cancer with signet-ring cells to the
stomach and review the literature.
Materials and methods. Case report 1: A 63-year old female went
to gastroenterology consultation complaining of aspecific gastrointestinal
symptoms. Abdominal CT scan showed thickening of
the gastric wall without focal thoracic or abdominal lesions. Upper
gastrointestinal endoscopy showed friable mucosa with two ulcers
at the antrum and body in a background of linitis plastica. Biopsies
of the antrum, body and gastric fundus were performed.
Case report 2: A 64-year old female underwent mastectomy of
the right breast for lobular carcinoma with positive margins (staging
not available) at an outside institution. The patient performed
adjuvant chemotherapy in the same year. Two years later, the
patient represented complaining of vague gastrointestinal symptoms.
Abdominal RMI scan showed thickening of the gastric
wall with severe stenosis, concentric thickening of rectal wall.
Upper gastrointestinal endoscopy showed erythematous mucosa,
evidence of linitis plastica, with marked stenosis of the lumen.
Sigmoidoscopy showed erythematous and edematous mucosa
with thickened wall and a biopsy of the rectum was performed.
She underwent a partial gastrectomy because of severe gastric
stenosis during the same admission.
Results. Case report 1: Gastric biopsies revealed the presence
of poorly differentiated carcinoma. The neoplastic cells had eosinophilic
cytoplasm with signet-ring appearance and hyperchromatic
nucleus. Cells were non cohesive and dispersed in single
elements. A first diagnosis of diffuse type non cohesive gastric
cancer was made. Further clinical information revealed that earlier
the same year, the patient had been diagnosed with a lobular
breast carcinoma with axillary lymphadenopathy on VABB core
biopsy of a mass in her left breast (staging not available) at a
different institution. The primary breast carcinoma showed the
following immunohistochemistry (IHC) profile: Cytokeratin
7 (CK7) positive, Cytokeratin 34βE12 positive, E-Cadherin
CONGRESSO aNNualE di aNatOmia patOlOGiCa SiapEC – iap • fiRENzE, 25-27 OttOBRE 2012
positive, Estrogen receptor (ER) positive, Cytokeratin 20 (CK20)
negative and Progesterone receptor (PgR) negative. The gastric
neoplastic cells also stained positive with CK 7, Cytokeratin
34βE12, gross cystic disease fluid protein-15 (GCDFP-15) and
ER. Neoplastic cells were negative for CK20, for E-Cadherin
and for PgR. The diagnosis of metastatic lobular carcinoma (with
signet-ring cells) to stomach was made.
Case report 2: Histological examination of rectal biopsies showed
the presence of isolated neoplastic elements, with signet-ring appearance
in the lamina propria. Further clinical information was
sought and only at this point was information of a previous breast
primary and of gastric wall thickening given to the pathologist.
IHC was therefore performed and this showed expression of
CK7, Cytokeratin 34βE12, GCDFP-15 and ER. Neoplastic cells
were negative for CK20, for caudal type homeobox transcription
factor 2 (CDX2) and for PgR. Histological examination of the
gastric specimen showed severe luminal stenosis due to diffuse
infiltration of atypical cells with signet-ring cells morphology.
IHC showed the same immunoprofile. The diagnosis of metastatic
lobular carcinoma (with signet-ring cells) to stomach and
rectum was made.
Discussion. Breast cancer is the most frequent malignant tumor
to metastasize to the gastrointestinal tract in women and is second
only to malignant melanoma 3 . Metastatic invasive lobular
carcinoma can mimic gastric cancer 4 5 and incidence of breast
cancer metastasis to the stomach in long term follow up and post
mortem studies has been estimated at 2–18% 6 7 . It is important
to remember that metastatic spread may be seen years after the
diagnosis of the primary breast lesion.
Distinction between metastatic lobular breast cancer and diffuse
type gastric cancer is possible only with adequate clinical information
and an immunohistochemical panel. Metastatic breast
carcinoma is usually positive for CK7, GCDFP-15, ER and PgR
and negative for CK20. CK20 proves to be useful as it is positive
in gastric cancer while it is not observed in breast carcinomas 8 .
CK7 is less useful as it is expressed in 90% of breast carcinomas
and its expression was also observed in 50-64% of primary
gastric adenocarcinoma 9 . Although primary gastric cancer has
been reported to show ER and PgR positivity 10 , Van Velthuysen
et al. 11 report that ERα can be reliably used to diagnose gastric
metastasis from breast cancer because no primary gastric tumor
express ERα. They observe that the absence of E-cadherin staining
was significantly related to metastatic breast carcinoma 12 .
Furthermore, cytoplasmic positivity for GCDFP-15 may confirm
mammary origin. Positive staining with GCDFP-15 has been
found to be a sensitive (55-76%) and specific (95-100%) marker
for correctly identifying a malignant lesion as metastatic breast
carcinoma 13 . An excellent correlation between GCDFP-15
positivity and the origin of a metastatic breast adenocarcinoma
has been demonstrated. Mammoglobin is another marker, which
is more sensitive but less specific compared to GCDFP-15. In
conclusion a correct history of patients and histological examination
and immunohistochemical analysis of the gastrointestinal
biopsies in comparison with the original breast cancer histology
are essential to support the diagnosis of metastatic breast cancer
to gastrointestinal tract. Clinicians must therefore be aware of the
difficult differential diagnosis and must supply adequate clinical
information especially concerning any previous malignancy.
Case report n. 2. Rectal biopsy: A) (H&E) 40x; B) CK7 40x; C)
CK20 40x; D) ER 40x; E) GCDFP15 40x. Gastric specimen: F)
H&E 40x; G) CK 7 10x; H) CK20 10x; I) ER 20x; GCDFP-15
20x.
references
1 Madeya S, Borsch G. Gastrointestinal metastases of breast carcinoma.
Gastrointest Endoscopy 1993;39:103-4.
2 Arrangoiz R, Papavasiliou P, Dushkin H, et al. Report and literature
review: Metastatic lobular carcinoma of the breast an unusual presentation.
Int J Surg Case Rep 2011;2:301-5.