Introduction

Breast carcinoma has been considered a systemic disease since its onset. [1] It usually metastasizes to bone, lungs and the liver. [2,3] The central nervous system (CNS), endocrine organs (ovary, adrenal, pituitary), pericardium, abdominal cavity and eye are infrequently involved organs. [2] Breast carcinoma metastasizing to the gallbladder is extremely rare and only 4 cases have been reported in the English literature. [2,4,5] In a large autopsy series analysis, metastases to the gallbladder were found in only 5.8% of cancer patients. [6] The tumor which is most likely to metastasize to the gallbladder is malignant melanoma. [7] Breast carcinoma involves the gallblabber in only 4%-7% of patients. [8]

Case report

The patient was a 53-year-old lady with unknown significant co-morbidities who complained of a lump in the left breast for 3 weeks.  Fine needle aspiration cytology (FNAC) from the lump was done at another institute and ductal carcinoma was reported. The patient underwent modified radical mastectomy (MRM) with axillary clearance at the same institute. The result of histopathological examination (HPE) was suggestive of signet ring cell variant of lobular carcinoma of the left breast.  She was diagnosed as having lobular carcinoma, of the left breast (pT1N0M0, stage I). After MRM, she developed acute pain abdomen and had a similar episode of pain abdomen before the detection of the lump. Ultrasonography (USG) done at that time revealed obliterated lumen, wall thickening and calculus of the gallbladder. Computed tomography (CT) of the whole abdomen revealed gallbladder calculus and focal thickening, which were suspicious of a mitotic process. She underwent exploratory laparotomy with cholecystectomy. HPE revealed signet ring cell adenocarcinoma of the gallbladder with transmural penetration into the adjacent liver parenchyma. The patient was opined for having two primary malignancies. However, review of outside MRM and cholecystectomy slides done at our hospital was suggestive of signet ring variant of lobular carcinoma of the left breast with lymphatic invasion metastatic to the gallbladder and liver (Fig.). In view of uncommon metastatic site, the slides and paraffin blocks of MRM and cholecystectomy were reviewed at the Mclaren Regional Cancer Centre, Flint, MI, USA, and they also suggested the diagnosis of signet ring cell variant of lobular carcinoma of the breast metastatic to the gallbladder and liver, confirmed by immunohistochemistry (IHC) positive for BCA-225 (CA 15.3) at both sites, breast and gallbladder. She was finally diagnosed as having carcinoma of the left breast metastatic to the gallbladder and liver and was started on taxane and anthracycline-based palliative chemotherapy. Revaluation after 4 cycles of chemotherapy revealed an abnormal area of increased radiotracer uptake in the right occipital region and the left 4th rib posteriorly on bone scanning. MRI of the brain revealed a focal enhancing lesion in the right frontal and left parietal region suggestive of metastasis. The patient was started on palliative radiotherapy to the brain along with a triple intrathecal therapy. Despite all the measures, her general condition deteriorated and was discharged for further palliative supportive care at home. She was lost to follow up after the discharge and died one month later.

Discussion

Breast carcinoma is associated with contiguous, lymphatic and hematogenous spread, and usually metastasizes to bone, lungs and the liver. [2,3] Signet ring cell carcinoma of the breast is considered a morphologic variant of infiltrating lobular carcinoma, with a poorer prognosis. Signet ring cells are also found in infiltrating ductal carcinoma and pure signet ring cell carcinoma of the breast has also been described. [3] The signet ring cells are characterized by a large mucin containing vacuoles pushing the nucleus to the periphery. Although signet ring cells are typically seen in malignancies of the gastrointestinal tract, their cytomorphological manifestations may also present in the breast, endometrial carcinoma, adenomatoid tumor of the endometrium as well as in postmenopausal idiopathic decidual reaction. [3] Cytokeratin (CK) 20 and CK7 are usually used for identification of the origin of metastatic signet ring cell carcinoma. In gastrointestinal primary carcinoma, CK20 is positive but CK7 is negative; in contrast, in metastatic breast carcinoma CK7 is positive but CK20 is negative. [3]

The occurrence of metastases to the gallbladder is rare and has only been reported in the literature exceptionally. [2,9-11] In one large autopsy series, metastases to the gallbladder were found only in 5.8% of cancer patients. [6] The tumor which is most likely to metastasize to the gallbladder is malignant melanoma. [7] However, small bowel is the most frequent site of metastatic melanoma in the gastrointestinal tract, and gallbladder involvement occurs in 15% of the cases. [7,12]

Primary tumors can metastasize to the gallbladder either by direct invasion of the porta hepatis or by hematogenous spread. [13,14] Hematogenous spread to the gallbladder has been found to be associated with melanoma and other primary tumors such as renal cell, cervical, gastric, lung, and breast carcinomas. [4]

In the previously reported cases, metastatic breast carcinoma involving the gallbladder or biliary tract, patients presented with abdominal pain, symptoms of acute or chronic cholecystitis and obstructive jaundice. [4,10,15] Gutknecht et al [11] reported a 69-year-old patient with inoperable lung cancer who later developed cholecystitis owing to metastasis to the gallbladder wall. Beaver et al [2] reported a 73-year-old lady with breast carcinoma who developed cholecystitis and subsequently underwent cholecystectomy. The result of HPE was consistent with metastatic carcinoma from primary breast carcinoma. Similarly, Crawford et al [5] reported two cases of metastatic carcinoma breast presenting as cholecystitis. Both patients had undergone mastectomy years earlier. HPE of cholecystectomy specimens revealed metastatic infiltrating ductal carcinoma in one patient and infiltrating lobular carcinoma in the other. [5]

In conclusion, metastatic gallbladder involvement is rare, especially with primary breast carcinoma. It usually leads to symptoms of pain abdomen, mimicking acute or chronic cholecystitis and obstructive jaundice. Its prognosis is poor after the development of gallbladder metastases. Thus, pain abdomen in the patient with breast carcinoma should be suspicious of metastatic gallbladder and treated aggressively as it portends a poor prognosis.

Funding: None.

Ethical approval: Not needed.

Contributors: DDC, BK and SJB did the primary conceptualization, clinical treatment and writing of the manuscript. VAK and PK reviewed the manuscript. HD did the histopatholgical aspect.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

References

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Received November 21, 2005

Accepted after revision March 7, 2006