Int Urol Nephrol DOI 10.1007/s11255-014-0660-y
UROLOGY - CASE REPORT
A collecting duct carcinoma producing carcinoembryonic antigen and Ca-125 in a 29-year-old woman Nikolaos Tsoukalas • Ioannis D. Kostakis • Maria Tolia • Dimitrios Tryfonopoulos Georgios Lypas • Christos Panopoulos • Vasileios Barbounis • Georgios Koumakis Anna Efremidis
• •
Received: 12 November 2013 / Accepted: 29 January 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract Collecting duct carcinoma is a rare renal malignant neoplasm, arising from the medullary collecting duct and accounting for less than 1 % of renal cell carcinomas. It is more common in middle-aged men and is usually presented with hematuria, abdominal mass and back or flank pain. Its immunohistochemical analysis detects the expression of various markers, such as low and high molecular weight keratins, Ulex europaeus agglutinin1, epithelial membrane antigen and peanut lectin. Here, we present a case of a 29-year-old woman with CDC presented with back pain and supraclavicular lymphadenopathy that produced carcinoembryonic antigen and CA-125.
Introduction
Keywords Collecting duct carcinoma Bellini’s tumor Renal cancer Carcinoembryonic antigen CEA CA-125
A 29-year-old woman was admitted to our department due to back pain, dating from 3 months ago, and fever. Clinical examination revealed the presence of enlarged left supraclavicular lymph nodes. The imaging studies, which included an abdominal computed tomography (CT)
Collecting duct carcinoma (CDC) (or Bellini’s tumor) is a rare renal malignant neoplasm arising from the epithelial cells of the medullary collecting duct [1–6]. Here, we present a case of a 29-year-old woman with CDC presented with back pain and supraclavicular lymphadenopathy that produced carcinoembryonic antigen (CEA) and CA-125.
Case report
N. Tsoukalas M. Tolia D. Tryfonopoulos G. Lypas C. Panopoulos V. Barbounis G. Koumakis A. Efremidis Second Department of Medical Oncology, ‘‘Agios Savvas’’ Anticancer Hospital, 171 Alexandras Avenue, 11522 Athens, Greece N. Tsoukalas Department of Medical Oncology, ‘‘401’’ General Military Hospital, 138 Mesogeion Avenue and Katehaki Avenue, 11525 Athens, Greece I. D. Kostakis Second Department of Propaedeutic Surgery, ‘‘Laiko’’ General Hospital, Medical School, National and Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527 Athens, Greece I. D. Kostakis (&) 27 Achridos Street, Kato Patissia, 11144 Athens, Greece e-mail: [email protected]
Fig. 1 Abdominal computed tomography
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Int Urol Nephrol Fig. 2 Positron emission tomography/computed tomography
(Fig. 1) and positron emission tomography (PET)/CT (Fig. 2), showed a mass with necrotic areas, 4 cm in diameter, which was originated from the upper pole of the right kidney and was in close proximity to the inferior vena cava and the right renal vessels. Enlarged para-aortic lymph nodes were also detected at the level of the lower pole of the right kidney, encircling, displacing and compressing the inferior vena cava, which had an unclear outline, indicating its infiltration by the neoplasm. Blood tests revealed increased serum levels of CEA (71.3 ng/ml, normal values: \3.4 ng/ml) and CA-125 (94.9 U/ml, normal values: \35 U/ml). Further studies, including chest CT, bone scan, bronchoscopy, gastrointestinal endoscopy,
123
gynecologic examination and transvaginal ultrasonography, revealed no additional abnormal findings. Fine needle aspiration of the left supraclavicular lymph nodes and the right renal mass showed the presence of adenocarcinoma. The tumor was considered initially inoperable due to the infiltration of the inferior vena cava by the neoplasm, whereas the left supraclavicular lymph nodes were excised. Their histopathological examination revealed the presence of a grade II metastatic adenocarcinoma with perinodal extracapsular extension (Fig. 3), and the immunohistochemical examination gave positive results for cytokeratin (CK) 7, CK8, CK18, CK19, Ulex europaeus agglutinin-1 (UEA-1) and epithelial membrane
Int Urol Nephrol
Fig. 3 Histological image of the metastatic lesion in the left supraclavicular nodes (2009 original magnification)
Fig. 4 Histological image of the primary tumor (1009 original magnification)
antigen (EMA). Therefore, the diagnosis of a CDC as the primary tumor was made. The patient received interferon and vinblastine, initially, and sunitinib, afterward, with a partial response to treatment, as indicated by the reduction in size of the primary and the para-aortic mass. Subsequently, the tumor was considered operable, and she underwent right radical nephrectomy, including excision of Gerota’s fascia, perirenal fat, right ureter and right adrenal gland and radical dissection of para-aortic lymph nodes. The histopathological examination of the surgical specimen showed the presence of a grade II carcinoma of distal nephron origin compatible with CDC (Figs. 4 and 5), expressing CK 7, CK8, CK18, CK19, UEA-1 and EMA and measuring 7 cm 9 7 cm 9 5 cm. The tumor invaded the renal
Fig. 5 Histological image of the primary tumor (2009 original magnification)
parenchyma and extended beyond the Gerota’s fascia, and three lymph nodes were infiltrated by the neoplasm (T4N1M1, stage IV). After the surgery, the patient continued the treatment with sunitinib. One month after nephrectomy, blood tests showed normal levels of CEA (2.9 ng/ml) and CA-125 (9.4 U/ml). Two months after nephrectomy, a CT scan showed a retroperitoneal mass surrounding the inferior vena cava and enlarged para-aortic and left supraclavicular lymph nodes, indicating a tumor relapse. Therefore, she underwent radiation therapy of the para-aortic and left supraclavicular fields combined with cisplatin, which yielded a major response. After the radiation treatment, she received chemotherapy including carboplatin and gemcitabine. Fourteen months after the radiation therapy, she underwent resection of the para-aortic mass, which had increased in size, along with wedge resection of an infiltrated part of the left lobe of the liver. The histological examination revealed the presence of relapse of the initial tumor. The patient received per os sorafenib after the surgery. She died 19 months later, after a new tumor recurrence at the original site, detected 1 year after the second operation, and gradual metastatic spread of the disease.
Discussion Renal cell carcinoma has five main histological subtypes: clear cell, papillary, chromophobe, collecting duct and unclassified [6]. CDC (or Bellini’s tumor), which arises from the epithelial cells of the medullary collecting duct [1–5], is the rarest among them, accounting for less than 1 % of the renal cell carcinomas [5, 6]. There is a wide
123
Int Urol Nephrol
patient age range in CDC [1, 3, 5], but it usually affects patients between the fourth and the seventh decade of life [5], with a mean age of 55 years [3, 5]. There is also a male preponderance with a male-to-female ration of about 2–1 [5]. CDC is usually presented with hematuria, flank or back pain and abdominal mass [1–3, 5]. General symptoms such as weight loss, fever and fatigue are also occasionally present [3, 5]. Due to the rapid growth and the early metastatic spread of these tumors, about one-third of the patients have already developed distant metastases at the time of diagnosis [5]. The most common site of metastasis is the lymph node [2], and cervical or supraclavicular lymph nodes are often involved [1, 2]. CDC is an aggressive neoplasm with poor prognosis [1–5], because about two-thirds of patients die within 2 years from diagnosis [1, 3, 5]. CDCs are generally firm, poorly circumscribed, white or gray tumors [1, 3, 5] consisted of eosinophilic cells [1, 2, 6–9]. There are various growth patterns, such as solid, tubular, papillary and cribriform [1–3, 5–9], and the nuclear atypia is prominent [2–5, 7–9]. The expression of various markers in immunohistochemical analysis, such as low and high molecular weight keratins, UEA-1, peanut lectin, EMA, E-cadherin and c-KIT, is suggestive of CDC [1, 3–6, 8, 9]. Regarding imaging studies, CDCs usually appear as a centrally arising tumor with low contrast enhancement and preservation of kidney contour [2, 7]. In our case, the tumor was not presented with hematuria [1–3, 5], but with back pain and supraclavicular lymphadenopathy. In addition, the tumor produced CEA and CA-125, which are characteristics of other types of cancers, such as colorectal cancer for CEA [10] and ovarian cancer for CA-125 [11], but not for CDC. The increased levels of CEA and CA-125 should be attributed to the CDC, because other potential causes were excluded by the paraclinical studies and their levels returned to normal 1 month after nephrectomy. We found only one case of CDC with increased serum levels of CEA and no case of CDC with increased serum levels of CA-125. Thus, CEA and CA-125 may be useful as potential markers of CDC in the future.
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Conflict of interest of interest.
The authors declare that they have no conflict
References 1. Matz LR, Latham BI, Fabian VA, Vivian JB (1997) Collecting duct carcinoma of the kidney: a report of three cases and review of the literature. Pathology 29:354–359 2. Milowsky MI, Rosmarin A, Tickoo SK, Papanicolaou N, Nanus DM (2002) Active chemotherapy for collecting duct carcinoma of the kidney: a case report and review of the literature. Cancer 94:111–116 3. Kuroda N, Toi M, Hiroi M, Enzan H (2002) Review of collecting duct carcinoma with focus on clinical and pathobiological aspects. Histol Histopathol 17:1329–1334 4. Orsola A, Trias I, Ravento´s CX, Espan˜ol I, Cecchini L, Orsola I (2005) Renal collecting (bellini) duct carcinoma dispalys similar characteristics to upper tract urothelial cell carcinoma. Urology 65:49–54 5. Srigley JR, Delahunt B (2009) Uncommon and recently described renal carcinomas. Mod Pathol 22:S2–S23 6. Truong LD, Shen SS (2011) Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med 135:92–109 7. Yoon SK, Nam KJ, Rha SH, Kim JK, Cho KS, Kim B, Kim KH, Kim KA (2006) Collecting duct carcinoma of the kidney: CT and pathologic correlation. Eur J Radiol 57:453–460 8. Gupta R, Billis A, Shah RB, Moch H, Osunkoya AO, Jochum W, Hes O, Bacchi CE, de Castro MG, Hansel DE, Zhou M, Vankalakunti M, Salles PG, Cabrera RA, Gown AM, Amin MB (2012) Carcinoma of the collecting ducts of Bellini and renal medullary carcinoma: clinicopathologic analysis of 52 cases of rare aggressive subtypes of renal cell carcinoma with a focus on their interrelationship. Am J Surg Pathol 36:1265–1278 9. Kobayashi N, Matsuzaki O, Shirai S, Aoki I, Yao M, Nagashima Y (2008) Collecting duct carcinoma of the kidney: an immunohistochemical evaluation of the use of antibodies for differential diagnosis. Hum Pathol 39:1350–1359 10. Hammarstro¨m S (1999) The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol 9:67–81 11. Nap M (1998) Immunohistochemistry of CA 125. Unusual expression in normal tissues, distribution in the human fetus and questions around its application in diagnostic pathology. Int J Biol Markers 13:210–215
UROLOGY - CASE REPORT
A collecting duct carcinoma producing carcinoembryonic antigen and Ca-125 in a 29-year-old woman Nikolaos Tsoukalas • Ioannis D. Kostakis • Maria Tolia • Dimitrios Tryfonopoulos Georgios Lypas • Christos Panopoulos • Vasileios Barbounis • Georgios Koumakis Anna Efremidis
• •
Received: 12 November 2013 / Accepted: 29 January 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract Collecting duct carcinoma is a rare renal malignant neoplasm, arising from the medullary collecting duct and accounting for less than 1 % of renal cell carcinomas. It is more common in middle-aged men and is usually presented with hematuria, abdominal mass and back or flank pain. Its immunohistochemical analysis detects the expression of various markers, such as low and high molecular weight keratins, Ulex europaeus agglutinin1, epithelial membrane antigen and peanut lectin. Here, we present a case of a 29-year-old woman with CDC presented with back pain and supraclavicular lymphadenopathy that produced carcinoembryonic antigen and CA-125.
Introduction
Keywords Collecting duct carcinoma Bellini’s tumor Renal cancer Carcinoembryonic antigen CEA CA-125
A 29-year-old woman was admitted to our department due to back pain, dating from 3 months ago, and fever. Clinical examination revealed the presence of enlarged left supraclavicular lymph nodes. The imaging studies, which included an abdominal computed tomography (CT)
Collecting duct carcinoma (CDC) (or Bellini’s tumor) is a rare renal malignant neoplasm arising from the epithelial cells of the medullary collecting duct [1–6]. Here, we present a case of a 29-year-old woman with CDC presented with back pain and supraclavicular lymphadenopathy that produced carcinoembryonic antigen (CEA) and CA-125.
Case report
N. Tsoukalas M. Tolia D. Tryfonopoulos G. Lypas C. Panopoulos V. Barbounis G. Koumakis A. Efremidis Second Department of Medical Oncology, ‘‘Agios Savvas’’ Anticancer Hospital, 171 Alexandras Avenue, 11522 Athens, Greece N. Tsoukalas Department of Medical Oncology, ‘‘401’’ General Military Hospital, 138 Mesogeion Avenue and Katehaki Avenue, 11525 Athens, Greece I. D. Kostakis Second Department of Propaedeutic Surgery, ‘‘Laiko’’ General Hospital, Medical School, National and Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527 Athens, Greece I. D. Kostakis (&) 27 Achridos Street, Kato Patissia, 11144 Athens, Greece e-mail: [email protected]
Fig. 1 Abdominal computed tomography
123
Int Urol Nephrol Fig. 2 Positron emission tomography/computed tomography
(Fig. 1) and positron emission tomography (PET)/CT (Fig. 2), showed a mass with necrotic areas, 4 cm in diameter, which was originated from the upper pole of the right kidney and was in close proximity to the inferior vena cava and the right renal vessels. Enlarged para-aortic lymph nodes were also detected at the level of the lower pole of the right kidney, encircling, displacing and compressing the inferior vena cava, which had an unclear outline, indicating its infiltration by the neoplasm. Blood tests revealed increased serum levels of CEA (71.3 ng/ml, normal values: \3.4 ng/ml) and CA-125 (94.9 U/ml, normal values: \35 U/ml). Further studies, including chest CT, bone scan, bronchoscopy, gastrointestinal endoscopy,
123
gynecologic examination and transvaginal ultrasonography, revealed no additional abnormal findings. Fine needle aspiration of the left supraclavicular lymph nodes and the right renal mass showed the presence of adenocarcinoma. The tumor was considered initially inoperable due to the infiltration of the inferior vena cava by the neoplasm, whereas the left supraclavicular lymph nodes were excised. Their histopathological examination revealed the presence of a grade II metastatic adenocarcinoma with perinodal extracapsular extension (Fig. 3), and the immunohistochemical examination gave positive results for cytokeratin (CK) 7, CK8, CK18, CK19, Ulex europaeus agglutinin-1 (UEA-1) and epithelial membrane
Int Urol Nephrol
Fig. 3 Histological image of the metastatic lesion in the left supraclavicular nodes (2009 original magnification)
Fig. 4 Histological image of the primary tumor (1009 original magnification)
antigen (EMA). Therefore, the diagnosis of a CDC as the primary tumor was made. The patient received interferon and vinblastine, initially, and sunitinib, afterward, with a partial response to treatment, as indicated by the reduction in size of the primary and the para-aortic mass. Subsequently, the tumor was considered operable, and she underwent right radical nephrectomy, including excision of Gerota’s fascia, perirenal fat, right ureter and right adrenal gland and radical dissection of para-aortic lymph nodes. The histopathological examination of the surgical specimen showed the presence of a grade II carcinoma of distal nephron origin compatible with CDC (Figs. 4 and 5), expressing CK 7, CK8, CK18, CK19, UEA-1 and EMA and measuring 7 cm 9 7 cm 9 5 cm. The tumor invaded the renal
Fig. 5 Histological image of the primary tumor (2009 original magnification)
parenchyma and extended beyond the Gerota’s fascia, and three lymph nodes were infiltrated by the neoplasm (T4N1M1, stage IV). After the surgery, the patient continued the treatment with sunitinib. One month after nephrectomy, blood tests showed normal levels of CEA (2.9 ng/ml) and CA-125 (9.4 U/ml). Two months after nephrectomy, a CT scan showed a retroperitoneal mass surrounding the inferior vena cava and enlarged para-aortic and left supraclavicular lymph nodes, indicating a tumor relapse. Therefore, she underwent radiation therapy of the para-aortic and left supraclavicular fields combined with cisplatin, which yielded a major response. After the radiation treatment, she received chemotherapy including carboplatin and gemcitabine. Fourteen months after the radiation therapy, she underwent resection of the para-aortic mass, which had increased in size, along with wedge resection of an infiltrated part of the left lobe of the liver. The histological examination revealed the presence of relapse of the initial tumor. The patient received per os sorafenib after the surgery. She died 19 months later, after a new tumor recurrence at the original site, detected 1 year after the second operation, and gradual metastatic spread of the disease.
Discussion Renal cell carcinoma has five main histological subtypes: clear cell, papillary, chromophobe, collecting duct and unclassified [6]. CDC (or Bellini’s tumor), which arises from the epithelial cells of the medullary collecting duct [1–5], is the rarest among them, accounting for less than 1 % of the renal cell carcinomas [5, 6]. There is a wide
123
Int Urol Nephrol
patient age range in CDC [1, 3, 5], but it usually affects patients between the fourth and the seventh decade of life [5], with a mean age of 55 years [3, 5]. There is also a male preponderance with a male-to-female ration of about 2–1 [5]. CDC is usually presented with hematuria, flank or back pain and abdominal mass [1–3, 5]. General symptoms such as weight loss, fever and fatigue are also occasionally present [3, 5]. Due to the rapid growth and the early metastatic spread of these tumors, about one-third of the patients have already developed distant metastases at the time of diagnosis [5]. The most common site of metastasis is the lymph node [2], and cervical or supraclavicular lymph nodes are often involved [1, 2]. CDC is an aggressive neoplasm with poor prognosis [1–5], because about two-thirds of patients die within 2 years from diagnosis [1, 3, 5]. CDCs are generally firm, poorly circumscribed, white or gray tumors [1, 3, 5] consisted of eosinophilic cells [1, 2, 6–9]. There are various growth patterns, such as solid, tubular, papillary and cribriform [1–3, 5–9], and the nuclear atypia is prominent [2–5, 7–9]. The expression of various markers in immunohistochemical analysis, such as low and high molecular weight keratins, UEA-1, peanut lectin, EMA, E-cadherin and c-KIT, is suggestive of CDC [1, 3–6, 8, 9]. Regarding imaging studies, CDCs usually appear as a centrally arising tumor with low contrast enhancement and preservation of kidney contour [2, 7]. In our case, the tumor was not presented with hematuria [1–3, 5], but with back pain and supraclavicular lymphadenopathy. In addition, the tumor produced CEA and CA-125, which are characteristics of other types of cancers, such as colorectal cancer for CEA [10] and ovarian cancer for CA-125 [11], but not for CDC. The increased levels of CEA and CA-125 should be attributed to the CDC, because other potential causes were excluded by the paraclinical studies and their levels returned to normal 1 month after nephrectomy. We found only one case of CDC with increased serum levels of CEA and no case of CDC with increased serum levels of CA-125. Thus, CEA and CA-125 may be useful as potential markers of CDC in the future.
123
Conflict of interest of interest.
The authors declare that they have no conflict
References 1. Matz LR, Latham BI, Fabian VA, Vivian JB (1997) Collecting duct carcinoma of the kidney: a report of three cases and review of the literature. Pathology 29:354–359 2. Milowsky MI, Rosmarin A, Tickoo SK, Papanicolaou N, Nanus DM (2002) Active chemotherapy for collecting duct carcinoma of the kidney: a case report and review of the literature. Cancer 94:111–116 3. Kuroda N, Toi M, Hiroi M, Enzan H (2002) Review of collecting duct carcinoma with focus on clinical and pathobiological aspects. Histol Histopathol 17:1329–1334 4. Orsola A, Trias I, Ravento´s CX, Espan˜ol I, Cecchini L, Orsola I (2005) Renal collecting (bellini) duct carcinoma dispalys similar characteristics to upper tract urothelial cell carcinoma. Urology 65:49–54 5. Srigley JR, Delahunt B (2009) Uncommon and recently described renal carcinomas. Mod Pathol 22:S2–S23 6. Truong LD, Shen SS (2011) Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med 135:92–109 7. Yoon SK, Nam KJ, Rha SH, Kim JK, Cho KS, Kim B, Kim KH, Kim KA (2006) Collecting duct carcinoma of the kidney: CT and pathologic correlation. Eur J Radiol 57:453–460 8. Gupta R, Billis A, Shah RB, Moch H, Osunkoya AO, Jochum W, Hes O, Bacchi CE, de Castro MG, Hansel DE, Zhou M, Vankalakunti M, Salles PG, Cabrera RA, Gown AM, Amin MB (2012) Carcinoma of the collecting ducts of Bellini and renal medullary carcinoma: clinicopathologic analysis of 52 cases of rare aggressive subtypes of renal cell carcinoma with a focus on their interrelationship. Am J Surg Pathol 36:1265–1278 9. Kobayashi N, Matsuzaki O, Shirai S, Aoki I, Yao M, Nagashima Y (2008) Collecting duct carcinoma of the kidney: an immunohistochemical evaluation of the use of antibodies for differential diagnosis. Hum Pathol 39:1350–1359 10. Hammarstro¨m S (1999) The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol 9:67–81 11. Nap M (1998) Immunohistochemistry of CA 125. Unusual expression in normal tissues, distribution in the human fetus and questions around its application in diagnostic pathology. Int J Biol Markers 13:210–215
