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Journal of Postgraduate Medicine
Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India
ISSN: 0022-3859 EISSN: 0972-2823
Vol. 51, Num. 2, 2005, pp. 125-127
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Journal of Postgraduate Medicine, Vol. 51, No. 2, April-June, 2005, pp. 125-127
Case Report
Breast metastases of gastric signet ring cell carcinoma: A differential diagnosis with primary breast signet ring cell carcinoma
Qureshi S.S., Shrikhande S.V., Tanuja S., Shukla P.J.
Departments of Surgical Gastroenterology, Tata Memorial Hospital, Parel, Mumbai
Correspondence Address: Departments of Surgical Gastroenterology,
Tata Memorial Hospital, Parel, Mumbai,
Email: pjshukla@doctors.org.uk
Date of Submission: 05-Sep-2004
Date of Decision: 30-Oct-2004
Date of Acceptance: 01-Nov-2004
Code Number: jp05049
ABSTRACT Metastatic deposits within the breast may be difficult to distinguish from primary breast carcinoma. Radiological features and immunohistochemistry especially for steroid hormone receptors and expression of gross cystic disease fluid protein may be helpful in differentiating these two conditions. In this report, we present a case of signet ring cell stomach cancer with metastasis to the breast and discuss the differential diagnostic options.
Keywords: Signet ring cell carcinoma, breast metastases, stomach neoplasm
Metastases in the breast from extra-mammary sites are uncommon with the incidence ranging from 1.7% to 6.6% in autopsy series and 1.2-2% in clinical reports and being 2.7% in cytological series.[1]
Approximately 300 cases of breast metastases from extra-mammary sites have been reported, mostly in small series or as single cases.[2] Gastric cancer metastases to the breast are rare with only 23 cases reported in the literature. [1],[2],[3],[4],[5],[6],[7],[8]
We report an exceptionally rare case of a gastric signet ring cell carcinoma (SRCC) metastasising to the breast and discuss the features differentiating metastatic gastric SRCC from primary SRCC of the breast.
Case History
A 34-year-old lactating woman presented with pain in the right hypochondrium and dysphagia. The patient also complained of a lump in the left breast. A similar swelling had appeared in the right breast one month before and had subsided with lactation and manual expression of milk.
Physical examination revealed a firm, 4x3 cm lump in the upper outer quadrant of the left breast without evidence of axillary or supraclavicular lymphadenopathy. The contralateral breast and axilla were normal. Gastrointestinal endoscopy showed a submucosal infiltrative lesion involving the proximal part of the stomach diagnosed as poorly differentiated adenocarcinoma on preoperative biopsy. Computerized tomographic (CT) scan of the abdomen showed thickening of the gastric wall. Mammography revealed heterogeneously dense breasts without any evidence of mass lesions, architectural distortion or microcalcifications
[Figure - 1]. Ultrasonography of the left breast was normal. With the exception of elevated carcinoembryonic antigen (CEA) to the level of 3.7, the tested blood parameters were normal.
Considering the clinical picture being consistent with primary cancer
of the stomach with a coexistent benign breast lesion, an explorative
laparotomy and a breast biopsy were planned. The patient underwent total
gastrectomy with Roux-en-Y oesophagojejunostomy via a left thoraco-abdominal
approach. No operative complications were observed. Excisional biopsy
of the breast lump showed metastasis of SRCC on frozen section.
Microscopic examination of the gastrectomy specimen revealed poorly
differentiated SRCC, infiltrating the full thickness of the stomach
with extensive perineural invasion and one out of ten perigastric lymph
nodes showing deposits of metastatic adenocarcinoma. The sections from
the breast lump revealed signet ring cells infiltrating the breast
stroma [Figure - 2].
The tumour cells were hardly seen on routine histology but were highlighted
by cytokeratin (CK) immunostaining and on staining the frozen sections
with toluidine blue. In the latter, the tumour cells showed pale blue
intracytoplasmic mucin indicating metastasis from a tumour of an organ
producing acidic mucin, like the stomach.
On immunohistochemistry(IHC), only a few tumour cells expressed CK
20, but all the cells were strongly positive for CK (antihuman cytokeratin,
reacting to a wide range of cytokeratin), epithelial membrane antigen
and CEA. GCDFP, CK 7, S-100 protein, oestrogen receptors (ER) and progesterone
receptors (PR) were negative. Special stains revealed that the intracytoplasmic
mucin was mucicarmine and alcian blue positive. The special stains
and the IHC profile of the stomach carcinoma were identical supporting
the diagnosis of metastatic gastric carcinoma in the breast.
The patient received chemotherapy (a combination of Paclitaxel and
Carboplatin). Ten days after completion of the first cycle of chemotherapy,
she developed a lump in her right breast as well as an infected seroma
in the operated left breast and febrile neutropenia. Antibiotics were
administered and any further chemotherapy withheld. In view of poor
general condition and progressive disease, only symptomatic treatment
was then offered. The patient died six months after the surgery.
DISCUSSION
The breast is a relatively uncommon site of metastases from extramammary primary malignancies. The average age of patients at the time of presentation of metastases is 47 years.[2] The relatively younger age of women with metastases in the breast suggests that the physiological state of the breast may provide a fertile soil for metastases.[3]
The metastatic lesions are usually palpable and most often located in the upper outer quadrant of the left breast.[2],[3],[4] Multiple, diffuse and bilateral involvement is rare as also is the involvement of the axillary lymph nodes.[2],[3],[4]
On mammography, the metastatic lesions may appear as well circumscribed masses which are difficult to distinguish from fibroadenoma or other benign solid lesions. Spicules are absent as there is little or no desmoplastic reaction associated with the metastatic lesion. Microcalcifications are not a feature of the metastases but have been observed in metastatic ovarian carcinoma with psammoma bodies. Thus, the presence of spiculated lesion(s) and microcalcifications on the mammogram is consistent with primary breast carcinoma and it practically rules out the possibility of the metastatic character of a tumour in the breast. [3],[4],[5]
Kwak et al considered the absence of mass lesions or microcalcifications on mammography or ultrasonography to be typical of metastatic disease in patients with SRCC in the breast.[5]
The histopathological features suggestive of metastases in the breast include absence of in- situ carcinoma, which characterises the majority of primary breast cancers. The histological picture usually resembles the extramammary primary tumour and is not typical of breast carcinomas.
Metastases from stomach adenocarcinomas, on IHC, are usually positive for CEA and CK 20 and negative for GCDFP, ER, PR, and CK 7.[9],[10] By
combining the results of CK 20 and ER staining, all the metastases to the
breast could be properly classified in one study, as all the gastrointestinal
tumors expressed the CK 20+ / ER- pattern.[10]
SRCC of the breast is a unique variant of invasive lobular carcinoma constituting
2 to 4.5% of all types of breast cancer.[7],[9] It
occurs more commonly in postmenopausal women and reveals high incidence
of positivity for ER, PR and GCDFP (90%). Therefore, IHC expression
of these markers may be useful in delineating primary and metastatic SRCC
in the breast.[9]
Differentiating primary breast SRCC from mammary metastases from a stomach primary is crucial for the management of a patient and can eliminate unnecessary procedures such as radical surgery.
In conclusion, palpable breast lumps without typical radiological signs
of primary breast carcinoma in patients with gastric cancer should be
suspected of representing metastases. Signet ring cell type of metastatic
stomach cancer is difficult to delineate from primary signet ring cell
cancer of the breast on histology. Immunohistochemical reactions, especially
absence of GCDFP expression in the tumour cells are helpful in making
the proper diagnosis.
ACKNOWLEDGEMENT We thank Dr. Sanjay Ahire for his help in the preparation of this article.
REFERENCES
1. | Di Cosimo S, Ferretti G, Fazio N, Mandala M, Curigliano G, Bosari S, et al . Breast and ovarian metastatic localization of signet ring cell gastric carcinoma. Ann Oncol 2003;14:803-4. Back to cited text no. 1 |
2. | Hamby LS, McGrath PC, Cilbull ML, Schwartz RW. Gastric carcinoma metastatic to the breast. J Surg Oncol 1991;48:117-21. Back to cited text no. 2 |
3. | Alexander HR, Turnbull AD, Rosen PP. Isolated breast metastases from gastrointestinal carcinomas: Report of two cases. J Surg Oncol 1989;42:264-6. Back to cited text no. 3 [PUBMED] |
4. | Cavazzini G, Colpani F, Cantore M, Aitini E, Rabbi C, Taffurelli M, et al . Breast metastasis from gastric signet ring cell carcinoma, mimicking inflammatory carcinoma. A case report. Tumori 1993;79:450-3. Back to cited text no. 4 |
5. | Kwak JY, Kim EK, Oh KK. Radiologic findings of metastatic signet ring cell carcinoma to the breast from stomach. Yonsei Med J 2000;41:669-72. Back to cited text no. 5 [PUBMED] [FULLTEXT] |
6. | Park JM, Kwon JS, Gong G. Metastatic breast carcinoma from gastric cancer: A case report. J Korean Radiol Soc 1998;38:1139-41. Back to cited text no. 6 |
7. | Briest S, Horn LC, Haupt R, Schneider JP, Schneider U, Hockel M. Metastasizing signet ring cell carcinoma of the stomach-mimicking bilateral inflammatory breast cancer. Gynecol Oncol 1999;74:491-4. Back to cited text no. 7 [PUBMED] [FULLTEXT] |
8. | Friedrich T, Kellermann S, Leinung S. Atypical metastasis of stomach carcinoma. Zentralbl Chir 1997;122:117-21. Back to cited text no. 8 [PUBMED] |
9. | Raju U, Ma CK, Shaw A. Signet ring variant of lobular carcinoma of the breast: A clinicopathologic and immunohistochemical study. Mod Pathol 1993;6:516-20. Back to cited text no. 9 [PUBMED] |
10. | Tot T. The role of cytokeratins 20 and 7 and estrogen receptor analysis in separation of metastatic lobular carcinoma of the breast and metastatic signet ring cell carcinoma of the gastrointestinal tract. APMIS 2000;108:467-72. Back to cited text no. 10 [PUBMED] |
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