A Differential Diagnosis with Primary Breast Signet Ring Cell Carcinoma
Case Report www.jpgmonline.com Breast metastases of gastric signet ring cell carcinoma: A differential diagnosis with primary breast signet ring cell carcinoma
Qureshi SS, Shrikhande SV, Tanuja S,* Shukla PJ
Departments of Surgical ABSTRACT Gastroenterology and Metastatic deposits within the breast may be difficult to distinguish from primary breast carcinoma. Radiological *Pathology, Tata Memo- rial Hospital, Parel, features and immunohistochemistry especially for steroid hormone receptors and expression of gross cystic Mumbai, India 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. Correspondence: P. J. Shukla E-mail: [email protected]
Received : 05-09-04 Review completed : 30-10-04 Accepted : 01-11-04 PubMed ID : 16006706 J Postgrad Med 2005;51:125-7 KEY WORDS: Signet ring cell carcinoma, breast metastases, stomach neoplasm
etastases in the breast from extra-mammary sites are tion or microcalcifications [Figure 1]. Ultrasonography of the left M uncommon with the incidence ranging from 1.7% to breast was normal. With the exception of elevated carcinoembryonic 6.6% in autopsy series and 1.2-2% in clinical reports and being antigen (CEA) to the level of 3.7, the tested blood parameters were 2.7% in cytological series.[1] Approximately 300 cases of breast normal. metastases from extra-mammary sites have been reported, mostly in small series or as single cases.[2] Gastric cancer Considering the clinical picture being consistent with primary can- cer of the stomach with a coexistent benign breast lesion, an explora- metastases to the breast are rare with only 23 cases reported in tive laparotomy and a breast biopsy were planned. The patient un- [1-8] the literature. derwent total gastrectomy with Roux-en-Y oesophagojejunostomy via a left thoraco-abdominal approach. No operative complications were We report an exceptionally rare case of a gastric signet ring observed. Excisional biopsy of the breast lump showed metastasis of cell carcinoma (SRCC) metastasising to the breast and dis- cuss 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 hy- pochondrium 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 ex- pression of milk.
Physical examination revealed a firm, 4x3 cm lump in the upper outer quadrant of the left breast without evidence of axillary or supracla- vicular lymphadenopathy. The contralateral breast and axilla were normal. Gastrointestinal endoscopy showed a submucosal infiltra- tive lesion involving the proximal part of the stomach diagnosed as poorly differentiated adenocarcinoma on preoperative biopsy. Com- puterized tomographic (CT) scan of the abdomen showed thicken- Figure 1: Mediolateral oblique mammograms revealing dense glandular ing of the gastric wall. Mammography revealed heterogeneously dense breast. There is no evidence of mass, architectural distortion or breasts without any evidence of mass lesions, architectural distor- microcalcifications in the left breast
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SRCC on frozen section. located in the upper outer quadrant of the left breast.[2-4] Mul- tiple, diffuse and bilateral involvement is rare as also is the Microscopic examination of the gastrectomy specimen revealed poorly involvement of the axillary lymph nodes.[2-4] differentiated SRCC, infiltrating the full thickness of the stomach with extensive perineural invasion and one out of ten perigastric lymph On mammography, the metastatic lesions may appear as well nodes showing deposits of metastatic adenocarcinoma. The sections circumscribed masses which are difficult to distinguish from from the breast lump revealed signet ring cells infiltrating the breast stroma [Figure 2]. The tumour cells were hardly seen on routine his- fibroadenoma or other benign solid lesions. Spicules are ab- tology but were highlighted by cytokeratin (CK) immunostaining and sent as there is little or no desmoplastic reaction associated on staining the frozen sections with toluidine blue. In the latter, the with the metastatic lesion. Microcalcifications are not a fea- tumour cells showed pale blue intracytoplasmic mucin indicating ture of the metastases but have been observed in metastatic metastasis from a tumour of an organ producing acidic mucin, like ovarian carcinoma with psammoma bodies. Thus, the pres- the stomach. ence of spiculated lesion(s) and microcalcifications on the mammogram is consistent with primary breast carcinoma and On immunohistochemistry(IHC), only a few tumour cells expressed it practically rules out the possibility of the metastatic charac- CK 20, but all the cells were strongly positive for CK (antihuman ter of a tumour in the breast.[3-5] cytokeratin, reacting to a wide range of cytokeratin), epithelial mem- brane antigen and CEA. GCDFP, CK 7, S-100 protein, oestrogen receptors (ER) and progesterone receptors (PR) were negative. Spe- Kwak et al considered the absence of mass lesions or cial stains revealed that the intracytoplasmic mucin was mucicar- microcalcifications on mammography or ultrasonography to mine and alcian blue positive. The special stains and the IHC profile be typical of metastatic disease in patients with SRCC in the of the stomach carcinoma were identical supporting the diagnosis of breast.[5] metastatic gastric carcinoma in the breast. The histopathological features suggestive of metastases in the The patient received chemotherapy (a combination of Paclitaxel and breast include absence of in- situ carcinoma, which character- Carboplatin). Ten days after completion of the first cycle of chemo- ises the majority of primary breast cancers. The histological therapy, she developed a lump in her right breast as well as an in- picture usually resembles the extramammary primary tumour fected seroma in the operated left breast and febrile neutropenia. Antibiotics were administered and any further chemotherapy with- and is not typical of breast carcinomas. held. In view of poor general condition and progressive disease, only symptomatic treatment was then offered. The patient died six months Metastases from stomach adenocarcinomas, on IHC, are usu- after the surgery. ally 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 Discussion staining, all the metastases to the breast could be properly clas- sified in one study, as all the gastrointestinal tumors expressed The breast is a relatively uncommon site of metastases from the CK 20+ / ER- pattern.[10] extramammary primary malignancies. The average age of pa- tients at the time of presentation of metastases is 47 years.[2] SRCC of the breast is a unique variant of invasive lobular car- The relatively younger age of women with metastases in the cinoma constituting 2 to 4.5% of all types of breast cancer.[7,9] breast suggests that the physiological state of the breast may It occurs more commonly in postmenopausal women and re- provide a fertile soil for metastases.[3] veals high incidence of positivity for ER, PR and GCDFP (90%). Therefore, IHC expression of these markers may be The metastatic lesions are usually palpable and most often 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 manage- ment of a patient and can eliminate unnecessary procedures such as radical surgery.
In conclusion, palpable breast lumps without typical radiologi- cal 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 de- lineate 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 mak- ing the proper diagnosis.
Acknowledgement Figure 2: Photomicrograph showing signet ring cells infiltrating the stroma between breast lobules (arrow). H/E, x100 We thank Dr. Sanjay Ahire for his help in the preparation of this article.
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References carcinoma to the breast from stomach. Yonsei Med J 2000;41:669-72. 6. Park JM, Kwon JS, Gong G. Metastatic breast carcinoma from gastric can- cer: A case report. J Korean Radiol Soc 1998;38:1139-41. 1. Di Cosimo S, Ferretti G, Fazio N, Mandala M, Curigliano G, Bosari S, et al. 7. Briest S, Horn LC, Haupt R, Schneider JP, Schneider U, Hockel M. Breast and ovarian metastatic localization of signet ring cell gastric carci- Metastasizing signet ring cell carcinoma of the stomach-mimicking bilateral noma. Ann Oncol 2003;14:803-4. inflammatory breast cancer. Gynecol Oncol 1999;74:491-4. 2. Hamby LS, McGrath PC, Cilbull ML, Schwartz RW. Gastric carcinoma meta- 8. Friedrich T, Kellermann S, Leinung S. Atypical metastasis of stomach carci- static to the breast. J Surg Oncol 1991;48:117-21. noma. Zentralbl Chir 1997;122:117-21. 3. Alexander HR, Turnbull AD, Rosen PP. Isolated breast metastases from 9. Raju U, Ma CK, Shaw A. Signet ring variant of lobular carcinoma of the breast: gastrointestinal carcinomas: Report of two cases. J Surg Oncol 1989;42:264- A clinicopathologic and immunohistochemical study. Mod Pathol 1993;6:516- 6. 20. 4. Cavazzini G, Colpani F, Cantore M, Aitini E, Rabbi C, Taffurelli M, et al. Breast 10. Tot T. The role of cytokeratins 20 and 7 and estrogen receptor analysis in metastasis from gastric signet ring cell carcinoma, mimicking inflammatory separation of metastatic lobular carcinoma of the breast and metastatic sig- carcinoma. A case report. Tumori 1993;79:450-3. net ring cell carcinoma of the gastrointestinal tract. APMIS 2000;108:467- 5. Kwak JY, Kim EK, Oh KK. Radiologic findings of metastatic signet ring cell 72.
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Cutaneous lesions on the legs
A 34-year-old woman had several symmetrically located, well- circumscribed, non-ulcerating, waxy, red-brown plaques on her lower limbs [Figure 1]. The first lesion appeared 13 years ago. She was concerned about the cosmetic appearance.
Questions 1. What is the diagnosis? 2. What is the systemic association with this dermatosis? 3. How are these lesions managed?
Figure 1: The first of these multiple, symmetrically located lesions appeared as a small macule 13 years previously. Inset: Close-up view of the oldest For the answer check page number 130 lesion shows waxy appearance and telangiectasias
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