Correspondence
Unusual presentation of metastatic gall bladder cancer ABSTRACT To report the first case of rare isolated breast metastasis from carcinoma gall bladder. Single patient case report. A 35‑year‑old pre‑menopausal female presented with 2 * 2 cm right upper outer quadrant breast lump. Post‑mastectomy, histology confirmed it to be metastatic adenocarcinoma positive for both Cytokeratin (CK) 7 and CK20. Past history as told by the patient revealed that 2 years back, cholecystectomy was performed for gall stones, of which no histology reports were present; she had a port site scar recurrence which showed it to be adenocarcinoma. Adjuvant chemotherapy and radiotherapy was advised which the patient did not complete. This is probably the first case reported of isolated breast metastasis from gall bladder carcinoma, diagnosed retrospectively. It also highlights the importance of adjuvant treatment in gall bladder malignancy. KEY WORDS: Adenocarcinoma, adjuvant treatment, cholecystectomy, gall bladder carcinoma, metastasis
INTRODUCTION The breast is an uncommon site for metastatic disease from extramammary neoplasms. Autopsy series demonstrate an incidence of metastases from extramammary primaries to a total of 0.5‑6.6% of all breast malignancies.[1,2] It is well documented that the presence of breast metastases is a poor prognostic factor.[2,3] Here we are presenting a case where primary cancer (Gall bladder) has metastasized to breast [Figure 1]. CASE REPORT A 35‑year‑old premenopausal lady presented in 2010 with a gradually progressive lump in her right breast, upper outer quadrant, 2 × 2 cm in size, freely mobile, not fixed to skin and deeper tissues. The patient was advised for a mammography which was of Breast Imaging Reporting and Data System five category and Trucut biopsy showed evidence of metastatic adenocarcinoma. Family history was negative, on general examination a right side subcostal scar was present with two earlier gall bladder surgeries. She underwent right mastectomy with ipsilateral axillary dissection. Post‑operative histopathology confirmed the presence of metastatic adenocarcinoma which was positive for Cytokeratin (CK) 7 and CK20 on immunostaining [Figure 2a and b]. On thoroughly investigating her past history it was revealed that she had undergone laparoscopic cholecystectomy in 2008 for management of gallstones. No
post‑operative histopathologic examination had been done at that time. After 1 year of the surgery she presented with multiple nodules over the port site and biopsy from those nodules were suggestive of adenocarcinoma. She underwent exploratory laparotomy and excision of port site metastases. Post‑operative histopathology was confirmatory of metastatic adenocarcinoma and the primary was most likely from the gall bladder. She was planned for adjuvant chemoradiation but she defaulted. This histopathologic finding in the above‑said clinical background was highly consistent with diagnosis of carcinoma gall bladder as the most likely primary. So she was again planned for adjuvant radiation to the chest wall concurrent with chemotherapy using Gemcitabine and Carboplatin although again she defaulted after two cycles of chemotherapy.
Piyush Shukla, Soumyajit Roy, Vivek Tiwari1, Bidhu K. Mohanti Department of Radiation Oncology, Institute Rotary Cancer Hospital, AIIMS, New Delhi, 1Department of Radiation Oncology, MIMS, Rewari, Haryana, India For correspondence: Dr. Piyush Shukla, Hostel No. 7, Room No. 10, Ansari Nagar, AIIMS, New Delhi ‑ 110 029, India. E‑mail: peeyush. [email protected]
DISCUSSION AND REVIEW OF LITERATURE A diversity of origins of metastases to the breast has been reported in the literature, and several studies have attempted to classify sites of origin in order of frequency. The most recent review of the literature by Vizcaino et al. showed the following as the commonest primary tumor sources in order of decreasing frequency: lymphoma, melanoma, rhabdomyosarcoma, lung tumors, and ovarian tumors. Recent study has reported that mean age of metastases to breast is 57.4 years. Metastases to the breast may occur years after the diagnosis of a primary cancer. The majority of metastases
Journal of Cancer Research and Therapeutics - April-June 2014 - Volume 10 - Issue 2
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.136669 PMID: *** Quick Response Code:
397
Shukla, et al.: Gall bladder cancer presenting as breast lump: Case study and review of literature
a
b
Figure 2: (a) Immunohistochemical nature of the epithelial cells which have shown positivity for Cytokeratin 7 activity (b) on immunostaining the epithelial cells are showing positivity for Cytokeratin 20 activity
behavior, even though there is no evidence to support this view at present.[10] Figure 1: Microscopic findings of the post-mastectomy specimen of the breast which is suggestive of glandular proliferation with collection of mucin in some of the glands’ lumen
is present as rapidly growing, painless, palpable, and firm breast masses.[3‑7] Up to 50% are found to be superficial[8] with no associated skin changes and with clinically palpable lymph nodes.[3,6] In our case the lump was painless without any palpable lymphadenopathy. Primary adenocarcinoma of the gallbladder spreads by extension and metastases, the former occurring earlier and more often. Direct contiguous extension of the lesion may occur by any of the four modes: Perivascular, intravascular, perineural, or by invasion of the nerve trunk proper. The liver is most frequently involved by direct extension, with an incidence ranging from 60% to 90%. Other organs commonly affected are the bile ducts, duodenum, stomach, colon, omentum, abdominal wall, pancreas, and portal vein. Metastases occur most frequently to the liver (76%‑86%), whereas regional lymph nodes are involved in about 60% of cases.[7] Extra‑abdominal metastasis is rare and the lung is the most common site. Rare sites of metastasis include the heart,[8] orbit, central nervous system, skin, bone, scalp, cervix, kidney, thyroid, and even the hernia sac. Metastasis to the breast from the gallbladder is probably by the hematogenous route. To the best of our knowledge there have been only two reported cases carcinoma gall bladder metastasizing to breast in the available English literature but in both the cases there was simultaneous metastasis to other organs, skin metastasis in the first case[9] and metastasis to ovary in the other respectively. The role of CK7 AND CK20 in establishing the diagnosis of the primary has been well documented in literature. Kalekou et al. have shown that CK7 expression was found in more than two thirds of Gall bladder cases, whereas CK20 expression was confined to less than one third of cases. They also speculated that CK20‑positive tumors may present a more aggressive
398
CONCLUSION This is probably the first reported case of isolated breast metastasis in a patient of carcinoma gall bladder, which depicts that, carcinoma gall‑bladder can have isolated metastasis to breast. Any lump in the breast in a known patient of carcinoma gall bladder should always be examined carefully using the full armory of clinical, radiologic, and pathologic examination. This case report, once again, proves the importance of adjuvant chemoradiation in carcinoma gall bladder without which it is impossible to stop the progression of this highly aggressive malignancy. REFERENCES 1. Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma; analysis of 1000 autopsied cases. Cancer 1950;3:74‑85. 2. McCrea ES, Johnston C, Haney PJ. Metastases to the breast. AJR Am J Roentgenol 1983;141:685‑90. 3. Amichetti M, Perani B, Boi S. Metastases to the breast from extramammary malignancies. Oncology 1990;47:257‑60. 4. Nunez DA, Sutherland CG, Sood RK. Breast metastasis from a pharyngeal carcinoma. J Laryngol Otol 1989;103:227‑8. 5. Masters A. Hypernephroma presenting as a lump in the breast. Aust N Z J Surg 1990;60:305‑6. 6. Hajdu SI, Urban JA. Cancers metastatic to the breast. Cancer 1972;29:1691‑6. 7. Garg PK, Khurana N, Hadke NS. Subcutaneous and breast metastasis from asymptomatic gallbladder carcinoma. Hepatobiliary Pancreat Dis Int 2009;8:209‑11. 8. Suganuma M, Marugami Y, Sakurai Y, Ochiai M, Hasegawa S, Imazu H, et al. Cardiac metastasis from squamous cell carcinoma of gallbladder. J Gastroenterol 1997;32:852‑6. 9. Singh S, Gupta P, Khanna R, Khanna AK. Simultaneous breast and ovarian metastasis from gallbladder carcinoma. Hepatobiliary Pancreat Dis Int 2010;9:553‑4. 10. Kalekou H, Miliaras D. Cytokeratin 7 and 20 expression in gallbladder carcinoma. Pol J Pathol 2011;62:25‑30. Cite this article as: Shukla P, Roy S, Tiwari V, Mohanti BK. Unusual presentation of metastatic gall bladder cancer. J Can Res Ther 2014;10:397-8. Source of Support: Nil, Conflict of Interest: All authors have completed the Unified Competing Interest form (available on request from corresponding author).
Journal of Cancer Research and Therapeutics - April-June 2014 - Volume 10 - Issue 2
Copyright of Journal of Cancer Research & Therapeutics is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Unusual presentation of metastatic gall bladder cancer ABSTRACT To report the first case of rare isolated breast metastasis from carcinoma gall bladder. Single patient case report. A 35‑year‑old pre‑menopausal female presented with 2 * 2 cm right upper outer quadrant breast lump. Post‑mastectomy, histology confirmed it to be metastatic adenocarcinoma positive for both Cytokeratin (CK) 7 and CK20. Past history as told by the patient revealed that 2 years back, cholecystectomy was performed for gall stones, of which no histology reports were present; she had a port site scar recurrence which showed it to be adenocarcinoma. Adjuvant chemotherapy and radiotherapy was advised which the patient did not complete. This is probably the first case reported of isolated breast metastasis from gall bladder carcinoma, diagnosed retrospectively. It also highlights the importance of adjuvant treatment in gall bladder malignancy. KEY WORDS: Adenocarcinoma, adjuvant treatment, cholecystectomy, gall bladder carcinoma, metastasis
INTRODUCTION The breast is an uncommon site for metastatic disease from extramammary neoplasms. Autopsy series demonstrate an incidence of metastases from extramammary primaries to a total of 0.5‑6.6% of all breast malignancies.[1,2] It is well documented that the presence of breast metastases is a poor prognostic factor.[2,3] Here we are presenting a case where primary cancer (Gall bladder) has metastasized to breast [Figure 1]. CASE REPORT A 35‑year‑old premenopausal lady presented in 2010 with a gradually progressive lump in her right breast, upper outer quadrant, 2 × 2 cm in size, freely mobile, not fixed to skin and deeper tissues. The patient was advised for a mammography which was of Breast Imaging Reporting and Data System five category and Trucut biopsy showed evidence of metastatic adenocarcinoma. Family history was negative, on general examination a right side subcostal scar was present with two earlier gall bladder surgeries. She underwent right mastectomy with ipsilateral axillary dissection. Post‑operative histopathology confirmed the presence of metastatic adenocarcinoma which was positive for Cytokeratin (CK) 7 and CK20 on immunostaining [Figure 2a and b]. On thoroughly investigating her past history it was revealed that she had undergone laparoscopic cholecystectomy in 2008 for management of gallstones. No
post‑operative histopathologic examination had been done at that time. After 1 year of the surgery she presented with multiple nodules over the port site and biopsy from those nodules were suggestive of adenocarcinoma. She underwent exploratory laparotomy and excision of port site metastases. Post‑operative histopathology was confirmatory of metastatic adenocarcinoma and the primary was most likely from the gall bladder. She was planned for adjuvant chemoradiation but she defaulted. This histopathologic finding in the above‑said clinical background was highly consistent with diagnosis of carcinoma gall bladder as the most likely primary. So she was again planned for adjuvant radiation to the chest wall concurrent with chemotherapy using Gemcitabine and Carboplatin although again she defaulted after two cycles of chemotherapy.
Piyush Shukla, Soumyajit Roy, Vivek Tiwari1, Bidhu K. Mohanti Department of Radiation Oncology, Institute Rotary Cancer Hospital, AIIMS, New Delhi, 1Department of Radiation Oncology, MIMS, Rewari, Haryana, India For correspondence: Dr. Piyush Shukla, Hostel No. 7, Room No. 10, Ansari Nagar, AIIMS, New Delhi ‑ 110 029, India. E‑mail: peeyush. [email protected]
DISCUSSION AND REVIEW OF LITERATURE A diversity of origins of metastases to the breast has been reported in the literature, and several studies have attempted to classify sites of origin in order of frequency. The most recent review of the literature by Vizcaino et al. showed the following as the commonest primary tumor sources in order of decreasing frequency: lymphoma, melanoma, rhabdomyosarcoma, lung tumors, and ovarian tumors. Recent study has reported that mean age of metastases to breast is 57.4 years. Metastases to the breast may occur years after the diagnosis of a primary cancer. The majority of metastases
Journal of Cancer Research and Therapeutics - April-June 2014 - Volume 10 - Issue 2
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.136669 PMID: *** Quick Response Code:
397
Shukla, et al.: Gall bladder cancer presenting as breast lump: Case study and review of literature
a
b
Figure 2: (a) Immunohistochemical nature of the epithelial cells which have shown positivity for Cytokeratin 7 activity (b) on immunostaining the epithelial cells are showing positivity for Cytokeratin 20 activity
behavior, even though there is no evidence to support this view at present.[10] Figure 1: Microscopic findings of the post-mastectomy specimen of the breast which is suggestive of glandular proliferation with collection of mucin in some of the glands’ lumen
is present as rapidly growing, painless, palpable, and firm breast masses.[3‑7] Up to 50% are found to be superficial[8] with no associated skin changes and with clinically palpable lymph nodes.[3,6] In our case the lump was painless without any palpable lymphadenopathy. Primary adenocarcinoma of the gallbladder spreads by extension and metastases, the former occurring earlier and more often. Direct contiguous extension of the lesion may occur by any of the four modes: Perivascular, intravascular, perineural, or by invasion of the nerve trunk proper. The liver is most frequently involved by direct extension, with an incidence ranging from 60% to 90%. Other organs commonly affected are the bile ducts, duodenum, stomach, colon, omentum, abdominal wall, pancreas, and portal vein. Metastases occur most frequently to the liver (76%‑86%), whereas regional lymph nodes are involved in about 60% of cases.[7] Extra‑abdominal metastasis is rare and the lung is the most common site. Rare sites of metastasis include the heart,[8] orbit, central nervous system, skin, bone, scalp, cervix, kidney, thyroid, and even the hernia sac. Metastasis to the breast from the gallbladder is probably by the hematogenous route. To the best of our knowledge there have been only two reported cases carcinoma gall bladder metastasizing to breast in the available English literature but in both the cases there was simultaneous metastasis to other organs, skin metastasis in the first case[9] and metastasis to ovary in the other respectively. The role of CK7 AND CK20 in establishing the diagnosis of the primary has been well documented in literature. Kalekou et al. have shown that CK7 expression was found in more than two thirds of Gall bladder cases, whereas CK20 expression was confined to less than one third of cases. They also speculated that CK20‑positive tumors may present a more aggressive
398
CONCLUSION This is probably the first reported case of isolated breast metastasis in a patient of carcinoma gall bladder, which depicts that, carcinoma gall‑bladder can have isolated metastasis to breast. Any lump in the breast in a known patient of carcinoma gall bladder should always be examined carefully using the full armory of clinical, radiologic, and pathologic examination. This case report, once again, proves the importance of adjuvant chemoradiation in carcinoma gall bladder without which it is impossible to stop the progression of this highly aggressive malignancy. REFERENCES 1. Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma; analysis of 1000 autopsied cases. Cancer 1950;3:74‑85. 2. McCrea ES, Johnston C, Haney PJ. Metastases to the breast. AJR Am J Roentgenol 1983;141:685‑90. 3. Amichetti M, Perani B, Boi S. Metastases to the breast from extramammary malignancies. Oncology 1990;47:257‑60. 4. Nunez DA, Sutherland CG, Sood RK. Breast metastasis from a pharyngeal carcinoma. J Laryngol Otol 1989;103:227‑8. 5. Masters A. Hypernephroma presenting as a lump in the breast. Aust N Z J Surg 1990;60:305‑6. 6. Hajdu SI, Urban JA. Cancers metastatic to the breast. Cancer 1972;29:1691‑6. 7. Garg PK, Khurana N, Hadke NS. Subcutaneous and breast metastasis from asymptomatic gallbladder carcinoma. Hepatobiliary Pancreat Dis Int 2009;8:209‑11. 8. Suganuma M, Marugami Y, Sakurai Y, Ochiai M, Hasegawa S, Imazu H, et al. Cardiac metastasis from squamous cell carcinoma of gallbladder. J Gastroenterol 1997;32:852‑6. 9. Singh S, Gupta P, Khanna R, Khanna AK. Simultaneous breast and ovarian metastasis from gallbladder carcinoma. Hepatobiliary Pancreat Dis Int 2010;9:553‑4. 10. Kalekou H, Miliaras D. Cytokeratin 7 and 20 expression in gallbladder carcinoma. Pol J Pathol 2011;62:25‑30. Cite this article as: Shukla P, Roy S, Tiwari V, Mohanti BK. Unusual presentation of metastatic gall bladder cancer. J Can Res Ther 2014;10:397-8. Source of Support: Nil, Conflict of Interest: All authors have completed the Unified Competing Interest form (available on request from corresponding author).
Journal of Cancer Research and Therapeutics - April-June 2014 - Volume 10 - Issue 2
Copyright of Journal of Cancer Research & Therapeutics is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
