J Gastrointest Canc (2015) 46:74–76 DOI 10.1007/s12029-014-9674-z
CASE REPORT
Rare Sites of Metastasis From Gall Bladder Carcinoma Supriya Mallick & Soumyajit Roy & Rony Benson & Sudeep Das & P. K. Julka & G. K. Rath
Published online: 4 December 2014 # Springer Science+Business Media New York 2014
Background Gall bladder carcinoma (GBC) is a relatively rare gastrointestinal tract malignancy in developed countries [1]. Epidemiology of this disease varies widely in different parts of the world and is one of the common malignancies of the female population in the northern part of India [2]. Radical cholecystectomy (RC) is often considered as the standard and adjuvant radio-chemotherapy is infrequently used. Even after a curative treatment, distant metastasis is the most common cause of progression. Liver and lung has been reported to be the commonest site [3]. Here in this report, we intend to report a few unusual sites of disease recurrence in a cohort of patients treated with curative approach.
oncologist, radiation oncologist, and medical oncologist. Patients were evaluated with contrast-enhanced computerized tomography (CECT) abdomen and pelvis, chest x-ray, complete blood count, liver, and renal functions. A radical or extended radical cholecystectomy was performed. A completion cholecystectomy was performed for patients attending clinic after inadvertent simple cholecystectomy for gall stone. Adjuvant Chemo Radiotherapy Protocol Adjuvant therapy was started within 4–6 weeks of surgery. Adjuvant external beam radiotherapy of 45 Gy in 25 fractions over 5 weeks was prescribed with concurrent and maintenance chemotherapy. Flurouracil 5-FU-based chemotherapy was most commonly used.
Methods Patient We retrospectively retrieved treatment charts of patients of GBC treated with curative intent in multidisciplinary gastrointestinal malignancy clinic. The demography, treatment details, and outcome data were retrieved in predesigned proforma. Surgery
Results Patients Six patients were identified to have unusual sites of metastasis. Five patients were found with the metastasis after curative treatment whereas one developed after palliative chemotherapy for metastatic disease. Median age was 52.5 years (range: 35–56 years). Patient characteristics and treatment details have been tabulated in Table 1.
The patients presenting de novo with radiological evidence of GBC were evaluated by a team of surgical
Surgery
S. Mallick (*) : S. Roy : R. Benson : S. Das : P. K. Julka : G. K. Rath Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India e-mail: [email protected]
Three patients presented with features of gall stone disease and underwent simple cholecystectomy (SC). Two patients were evaluated for malignancy and underwent radical cholecystectomy. Two patients had pathological T3N0 disease
J Gastrointest Canc (2015) 46:74–76 Table 1
Patient characteristic and treatment details
Patient Characteristics Age Sex Stage
Surgery Adjuvant RT dose Adjuvant chemotherapy
Status at last follow-up Site of recurrence
Median 52.5 (range 35–56 years) Female-6 IIIA-2 II-1 IV-1 Unknown-2 Simple cholecystectomy-3 Radical cholecystectomy-2 45 Gy/25 fractions/5 weeks GemOX-2 Oxaliplatin-1 Unknown-1 PD-4 Unknown/lost to follow-up-2 Lung, spleen, bone, orbit, vagina, brain
(stage IIIA), one had pT2No disease (stage II), stage was unknown for two patients, and one patient was diagnosed in stage IV.
75
Breast Metastasis from GBC Thirty-five-year-old premenopausal lady presented with 2× 2 cm lump in right breast, upper outer quadrant, freely mobile, and not fixed to skin and deeper tissues. The patient had a previous history of laparoscopic cholecystectomy. After 1 year of surgery, she presented with multiple nodules over the port site and biopsy from those nodules was suggestive of adenocarcinoma. She underwent exploratory laparotomy and excision of port site metastases. She was planned for adjuvant chemo-radiation but defaulted. Trucut biopsy from the breast lump showed evidence of metastatic adenocarcinoma (Fig. 1). This histopathologic finding in the above-said clinical background was highly consistent with diagnosis of carcinoma gall bladder. So, she was planned for radiation to the chest wall followed by chemotherapy with gemcitabine and carboplatin. However, she defaulted after 2 cycles of chemotherapy.
Orbital and Bone Metastasis from GBC
At a median follow-up of 25.7 months (11.4–72.3 months) these patients developed metastasis. We found one patient each with isolated metastasis to the bone, brain, and breast. The two other patients had metastasis to the vagina and spleen. However, these two cases had liver and lung metastasis also.
A 55-year-old lady presented with weakness for 1 month. On evaluation, CECT scan revealed thickening of neck of the gall bladder with peritoneal nodule and multiple liver lesion as well as celiac axis, portal, and peri pancreatic lymph node. FNAC from the gall bladder lesion revealed adenocarcinoma. She received 2 cycles of chemotherapy with gemcitabine and oxaliplatin. Subsequently, she developed left eye proptosis. Local examination revealed 3×3 cm swelling over left infratemporal fossa and proptosis of the left eye. A CECT of cranium revealed a lytic lesion in the left greater wing of sphenoid with soft tissue extending to the infra-temporal fossa. The CECT also revealed a soft tissue in the lateral extra-conal space indenting and medially displacing the lateral rectus muscle. The orbital and sphenoid lesion was treated with palliative radiotherapy 30 Gy in 10 fractions over 2 weeks by 3D-conformal radiotherapy technique. Similarly another
Fig. 1 a Glandular proliferation with collection of mucin in some of the glands’ lumen in a specimen of breast (×10), b c Immunohistochemistry (×200) showing reactive with CK7 and CK20; 2D, 2E-Axial CECT
image of orbit showing contrast enhancing mass in the extra-conal compartment of orbit as well as mass in the left greater wing of sphenoid with extension to infra-temporal fossa
Adjuvant Chemo Radiotherapy Protocol Adjuvant therapy was started within 4–6 weeks of surgery. Four patients received adjuvant external beam radiotherapy of 45 Gy in 25 fractions over 5 weeks was prescribed. Adjuvant chemotherapy was used in all but two cases. Recurrence After Adjuvant Treatment
76
patient developed multiple bone metastasis after a disease-free interval of 28 months.
Vagina Metastasis from GBC A 56-year-old female patient after completion of adjuvant treatment presented with peri-urethral growth. Per speculum examination revealed 3×4 cm ulcero proliferative growth in the anterior vaginal wall. Per vaginal examination revealed 3× 4 cm growth in anterior vaginal wall without extending to cervix or para-metrium. A biopsy from the growth revealed metastatic adenocarcinoma from gall bladder. The patient was treated with palliative radiotherapy to the vaginal lesion and palliative systemic chemotherapy.
Spleen Metastasis from GBC After treatment, she presented with hyper-bilirubinemia. A contrast-enhanced CT scan revealed left pleural effusion and moderate ascites and a single hypo-dense lesion in the spleen. The hypo-dense spleen lesion was solid and target shaped in USG correlation. The patient was considered suitable for any chemotherapy.
J Gastrointest Canc (2015) 46:74–76
It is important to understand the aggressive nature of gall bladder cancer and its possibility to metastasize in different organs by hematogenous spread. This gives us an important clue to aggressively evaluate patients with GBC. Hence, after adjuvant therapy, periodic evaluation of these patients is warranted with CECT abdomen and pelvis as well as chest x-ray. Imaging of other body parts may be guided by symptom. At the same time, it directs to revisit the issue of adjuvant radiotherapy and chemotherapy even after a successful surgical resection to optimize long-term disease control and survival.
Conclusion GBC is a very notorious malignancy with propensity for hematogenous route. It has the potential to spread in a wide range of organs even after curative treatment. Hence, adjuvant chemotherapy should be considered in GBC to optimize disease control and improve survival.
Disclosures The authors have nothing to disclose. Conflict of Interest The authors declare that they have no conflict of interest
Discussion Gall bladder carcinoma (GBC) is the fifth most common GI malignancy and the commonest malignancy of the biliary tract [1]. Surgery has long been considered the cornerstone of therapy. Adjuvant radio-chemotherapy is infrequently used. Even after curative treatment, systemic recurrence is the predominant cause of disease progression. Liver (75–86 %) and lung has been reported to be the commonest site of metastasis [3]. The most common site of extra abdominal metastasis is the lung. However, metastasis to bone, ovary, orbit, thyroid, and breast has also been reported very rarely [4–10]. But, a note should be made that often, such cases are reported in patients with advanced untreated cases. Here, we are reporting unusual sites of metastasis in a cohort of patients treated with curative approach as well as two cases with breast and orbital metastasis at presentation. We are, possibly for the first time, reporting a case of GBC with metastasis to vagina after 2 years of disease-free interval. Another patient in this cohort was found to have spleen metastasis after a disease-free interval of 11 months, which has also not been published earlier. The other sites of metastasis, breast, and bone have been reported anecdotally in the English literature [4–10]. But, these patients were all treated with curative resection followed by adjuvant radio-chemotherapy. It appears that hematogenous metastasis is the predominant cause of such progression.
References 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2007;57:43–66. 2. Three year report of the PBCRS 2006-2008; 2: 21 3. Bardaji M, Roset F, Puig A, Badal J, Fernandez-Layos MJ. Cutaneous metastatic adenocarcinoma of gallbladder origin: report of a case and review of the literature. Hepatogastroenterology. 1998;45:930–1. 4. Misra A, Misra S, Chaturvedi A, Srivastava PK. Case report. Orbital metastasis from gall bladder carcinoma. Br J Radiol. 2002;75(889): 72–3. 5. Puglisi F, Capuano P, Gentile A, Lobascio P, Russo S, Martines G, et al. Retrobulbar metastasis from gallbladder carcinoma after laparoscopic cholecystectomy. A case report. Tumori. 2005;91(5):428– 31. 6. Misra S, Chaturvedi A, Misra NC. Carcinoma gallbladder presenting with skeletal metastases. Indian J Gastroenterol. 1997;16(2):74. 7. Shukla P, Roy S, Tiwari V, Mohanti BK. Unusual presentation of metastatic gall bladder cancer. J Can Res Ther. 2014;10:397–8. 8. Garg PK, Khurana N, Hadke NS. Subcutaneous and breast metastasis from asymptomatic gallbladder carcinoma. Hepatobiliary Pancreat Dis Int. 2009;8:209–11. 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. 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.
CASE REPORT
Rare Sites of Metastasis From Gall Bladder Carcinoma Supriya Mallick & Soumyajit Roy & Rony Benson & Sudeep Das & P. K. Julka & G. K. Rath
Published online: 4 December 2014 # Springer Science+Business Media New York 2014
Background Gall bladder carcinoma (GBC) is a relatively rare gastrointestinal tract malignancy in developed countries [1]. Epidemiology of this disease varies widely in different parts of the world and is one of the common malignancies of the female population in the northern part of India [2]. Radical cholecystectomy (RC) is often considered as the standard and adjuvant radio-chemotherapy is infrequently used. Even after a curative treatment, distant metastasis is the most common cause of progression. Liver and lung has been reported to be the commonest site [3]. Here in this report, we intend to report a few unusual sites of disease recurrence in a cohort of patients treated with curative approach.
oncologist, radiation oncologist, and medical oncologist. Patients were evaluated with contrast-enhanced computerized tomography (CECT) abdomen and pelvis, chest x-ray, complete blood count, liver, and renal functions. A radical or extended radical cholecystectomy was performed. A completion cholecystectomy was performed for patients attending clinic after inadvertent simple cholecystectomy for gall stone. Adjuvant Chemo Radiotherapy Protocol Adjuvant therapy was started within 4–6 weeks of surgery. Adjuvant external beam radiotherapy of 45 Gy in 25 fractions over 5 weeks was prescribed with concurrent and maintenance chemotherapy. Flurouracil 5-FU-based chemotherapy was most commonly used.
Methods Patient We retrospectively retrieved treatment charts of patients of GBC treated with curative intent in multidisciplinary gastrointestinal malignancy clinic. The demography, treatment details, and outcome data were retrieved in predesigned proforma. Surgery
Results Patients Six patients were identified to have unusual sites of metastasis. Five patients were found with the metastasis after curative treatment whereas one developed after palliative chemotherapy for metastatic disease. Median age was 52.5 years (range: 35–56 years). Patient characteristics and treatment details have been tabulated in Table 1.
The patients presenting de novo with radiological evidence of GBC were evaluated by a team of surgical
Surgery
S. Mallick (*) : S. Roy : R. Benson : S. Das : P. K. Julka : G. K. Rath Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India e-mail: [email protected]
Three patients presented with features of gall stone disease and underwent simple cholecystectomy (SC). Two patients were evaluated for malignancy and underwent radical cholecystectomy. Two patients had pathological T3N0 disease
J Gastrointest Canc (2015) 46:74–76 Table 1
Patient characteristic and treatment details
Patient Characteristics Age Sex Stage
Surgery Adjuvant RT dose Adjuvant chemotherapy
Status at last follow-up Site of recurrence
Median 52.5 (range 35–56 years) Female-6 IIIA-2 II-1 IV-1 Unknown-2 Simple cholecystectomy-3 Radical cholecystectomy-2 45 Gy/25 fractions/5 weeks GemOX-2 Oxaliplatin-1 Unknown-1 PD-4 Unknown/lost to follow-up-2 Lung, spleen, bone, orbit, vagina, brain
(stage IIIA), one had pT2No disease (stage II), stage was unknown for two patients, and one patient was diagnosed in stage IV.
75
Breast Metastasis from GBC Thirty-five-year-old premenopausal lady presented with 2× 2 cm lump in right breast, upper outer quadrant, freely mobile, and not fixed to skin and deeper tissues. The patient had a previous history of laparoscopic cholecystectomy. After 1 year of surgery, she presented with multiple nodules over the port site and biopsy from those nodules was suggestive of adenocarcinoma. She underwent exploratory laparotomy and excision of port site metastases. She was planned for adjuvant chemo-radiation but defaulted. Trucut biopsy from the breast lump showed evidence of metastatic adenocarcinoma (Fig. 1). This histopathologic finding in the above-said clinical background was highly consistent with diagnosis of carcinoma gall bladder. So, she was planned for radiation to the chest wall followed by chemotherapy with gemcitabine and carboplatin. However, she defaulted after 2 cycles of chemotherapy.
Orbital and Bone Metastasis from GBC
At a median follow-up of 25.7 months (11.4–72.3 months) these patients developed metastasis. We found one patient each with isolated metastasis to the bone, brain, and breast. The two other patients had metastasis to the vagina and spleen. However, these two cases had liver and lung metastasis also.
A 55-year-old lady presented with weakness for 1 month. On evaluation, CECT scan revealed thickening of neck of the gall bladder with peritoneal nodule and multiple liver lesion as well as celiac axis, portal, and peri pancreatic lymph node. FNAC from the gall bladder lesion revealed adenocarcinoma. She received 2 cycles of chemotherapy with gemcitabine and oxaliplatin. Subsequently, she developed left eye proptosis. Local examination revealed 3×3 cm swelling over left infratemporal fossa and proptosis of the left eye. A CECT of cranium revealed a lytic lesion in the left greater wing of sphenoid with soft tissue extending to the infra-temporal fossa. The CECT also revealed a soft tissue in the lateral extra-conal space indenting and medially displacing the lateral rectus muscle. The orbital and sphenoid lesion was treated with palliative radiotherapy 30 Gy in 10 fractions over 2 weeks by 3D-conformal radiotherapy technique. Similarly another
Fig. 1 a Glandular proliferation with collection of mucin in some of the glands’ lumen in a specimen of breast (×10), b c Immunohistochemistry (×200) showing reactive with CK7 and CK20; 2D, 2E-Axial CECT
image of orbit showing contrast enhancing mass in the extra-conal compartment of orbit as well as mass in the left greater wing of sphenoid with extension to infra-temporal fossa
Adjuvant Chemo Radiotherapy Protocol Adjuvant therapy was started within 4–6 weeks of surgery. Four patients received adjuvant external beam radiotherapy of 45 Gy in 25 fractions over 5 weeks was prescribed. Adjuvant chemotherapy was used in all but two cases. Recurrence After Adjuvant Treatment
76
patient developed multiple bone metastasis after a disease-free interval of 28 months.
Vagina Metastasis from GBC A 56-year-old female patient after completion of adjuvant treatment presented with peri-urethral growth. Per speculum examination revealed 3×4 cm ulcero proliferative growth in the anterior vaginal wall. Per vaginal examination revealed 3× 4 cm growth in anterior vaginal wall without extending to cervix or para-metrium. A biopsy from the growth revealed metastatic adenocarcinoma from gall bladder. The patient was treated with palliative radiotherapy to the vaginal lesion and palliative systemic chemotherapy.
Spleen Metastasis from GBC After treatment, she presented with hyper-bilirubinemia. A contrast-enhanced CT scan revealed left pleural effusion and moderate ascites and a single hypo-dense lesion in the spleen. The hypo-dense spleen lesion was solid and target shaped in USG correlation. The patient was considered suitable for any chemotherapy.
J Gastrointest Canc (2015) 46:74–76
It is important to understand the aggressive nature of gall bladder cancer and its possibility to metastasize in different organs by hematogenous spread. This gives us an important clue to aggressively evaluate patients with GBC. Hence, after adjuvant therapy, periodic evaluation of these patients is warranted with CECT abdomen and pelvis as well as chest x-ray. Imaging of other body parts may be guided by symptom. At the same time, it directs to revisit the issue of adjuvant radiotherapy and chemotherapy even after a successful surgical resection to optimize long-term disease control and survival.
Conclusion GBC is a very notorious malignancy with propensity for hematogenous route. It has the potential to spread in a wide range of organs even after curative treatment. Hence, adjuvant chemotherapy should be considered in GBC to optimize disease control and improve survival.
Disclosures The authors have nothing to disclose. Conflict of Interest The authors declare that they have no conflict of interest
Discussion Gall bladder carcinoma (GBC) is the fifth most common GI malignancy and the commonest malignancy of the biliary tract [1]. Surgery has long been considered the cornerstone of therapy. Adjuvant radio-chemotherapy is infrequently used. Even after curative treatment, systemic recurrence is the predominant cause of disease progression. Liver (75–86 %) and lung has been reported to be the commonest site of metastasis [3]. The most common site of extra abdominal metastasis is the lung. However, metastasis to bone, ovary, orbit, thyroid, and breast has also been reported very rarely [4–10]. But, a note should be made that often, such cases are reported in patients with advanced untreated cases. Here, we are reporting unusual sites of metastasis in a cohort of patients treated with curative approach as well as two cases with breast and orbital metastasis at presentation. We are, possibly for the first time, reporting a case of GBC with metastasis to vagina after 2 years of disease-free interval. Another patient in this cohort was found to have spleen metastasis after a disease-free interval of 11 months, which has also not been published earlier. The other sites of metastasis, breast, and bone have been reported anecdotally in the English literature [4–10]. But, these patients were all treated with curative resection followed by adjuvant radio-chemotherapy. It appears that hematogenous metastasis is the predominant cause of such progression.
References 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2007;57:43–66. 2. Three year report of the PBCRS 2006-2008; 2: 21 3. Bardaji M, Roset F, Puig A, Badal J, Fernandez-Layos MJ. Cutaneous metastatic adenocarcinoma of gallbladder origin: report of a case and review of the literature. Hepatogastroenterology. 1998;45:930–1. 4. Misra A, Misra S, Chaturvedi A, Srivastava PK. Case report. Orbital metastasis from gall bladder carcinoma. Br J Radiol. 2002;75(889): 72–3. 5. Puglisi F, Capuano P, Gentile A, Lobascio P, Russo S, Martines G, et al. Retrobulbar metastasis from gallbladder carcinoma after laparoscopic cholecystectomy. A case report. Tumori. 2005;91(5):428– 31. 6. Misra S, Chaturvedi A, Misra NC. Carcinoma gallbladder presenting with skeletal metastases. Indian J Gastroenterol. 1997;16(2):74. 7. Shukla P, Roy S, Tiwari V, Mohanti BK. Unusual presentation of metastatic gall bladder cancer. J Can Res Ther. 2014;10:397–8. 8. Garg PK, Khurana N, Hadke NS. Subcutaneous and breast metastasis from asymptomatic gallbladder carcinoma. Hepatobiliary Pancreat Dis Int. 2009;8:209–11. 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. 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.
