Grand Rounds Metastatic Papillary Renal Cell Carcinoma Regression After Cytoreductive Nephrectomy Travis Williams, Robert Rodriguez, Katie Murray, Aaron Kovaleski, Rashna Madan, and Peter Van Veldhuizen
CASE PRESENTATION
A
previously healthy 69-year-old woman sought medical attention for stomach pain and distension associated with a 10-pound weight loss. There was no hematuria, fevers, chills, night sweats, or fatigue. Past medical history was significant for hypertension. In 1989, she required a temporary colostomy after a partial colectomy secondary to a colonic perforation. Family history was significant for a brother with glioblastoma multiforme, and her mother had kidney disease of unknown etiology. She did not report any previous chemical exposure but is a current smoker with a 45-pack year history of tobacco abuse. Initial kidney, ureter, and bladder imaging was done and suggested constipation. Pain control was achieved with an aggressive bowel regimen and pain medication, but the sensation of abdominal fullness persisted. On presentation to our clinic, vital signs were normal except for a 10-pound weight loss over a 3-week period. Physical examination revealed a left large, palpable, flank mass that was tender to palpation but no other palpable adenopathy. Her initial laboratory evaluation was significant for hemoglobin 10.3 g/dL, creatinine 1.17 mg/dL, calcium 10.0 mg/dL, albumin 4.0 g/dL, and lactate dehydrogenase 543 U/L (100-210 U/L). A computed tomography scan of the abdomen and pelvis followed by magnetic resonance imaging (MRI) of the abdomen revealed a 13.6 11.6 9.9 cm heterogeneous left renal mass (Fig. 1) with bulky retroperitoneal lymphadenopathy, left renal vein thrombus, a nonocclusive inferior vena caval tumor thrombus, ipsilateral adrenal gland Rashna Madan provided the pathologic description and pathology images for this case. Peter Van Veldhuizen is the senior author of this article and provided the discussion. Aaron Kovaleski provided the radiographic images and description, and Travis Williams, Robert Rodriguez, and Katie Murray were responsible for the remainder of the article. Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Hematology/Oncology, University of Kansas Medical Center, Kansas City, KS; the Department of Urology, University of Kansas Medical Center, Kansas City, KS; the Department of Radiology, University of Kansas Medical Center, Kansas City, KS; and the Department of Pathology, University of Kansas Medical Center, Kansas City, KS Address correspondence to: Travis Williams, D.O., Department of Hematology/ Oncology, University of Kansas Medical Center, 2330 Shawnee Mission Parkway Suite 210, Westwood, KS 66205. E-mail: [email protected] Submitted: May 12, 2014, accepted (with revisions): October 4, 2014
ª 2015 Elsevier Inc. All Rights Reserved
involvement, and innumerable hepatic and pulmonary metastasis measuring 5-10 and 3-5 mm, respectively (Figs. 2, 3). There was no evidence of cerebral or osseous metastasis on imaging studies.
DIFFERENTIAL DIAGNOSIS Several conditions were initially considered in the differential diagnosis. The imaging studies revealed metastatic disease involving lung, liver, kidney, and retroperitoneal adenopathy. Clear cell renal cell carcinoma was a consideration, given the large size of the left renal mass and inferior vena caval tumor thrombus. Metastatic carcinoma of likely ovarian or colonic origin was also considered. A concerning historical component was that her mother had been on dialysis for unexplained causes. Concern for an inherited familial renal malignancy such as von Hippel-Lindau syndrome, hereditary leiomyomatosis-associated renal cell cancer, Birt-Hogg-Dube syndrome, and hereditary papillary renal cancer were considered but felt unlikely given the patient’s age and lack of strong family history for malignancy.
MANAGEMENT AND OUTCOME She was referred for a palliative debulking nephrectomy, believing that her pain was secondary to the large left renal mass palpated on examination. The surgical procedures performed included left radical nephrectomy, retroperitoneal lymph node dissection, caval thrombectomy, splenectomy, and extensive lysis of adhesions. The nephrectomy revealed a 15.5 9.5 8.0 cm predominantly necrotic mass that obliterated the renal parenchyma and extended into the renal vein. Although the bulk of the tumor was necrotic with accompanying foamy macrophages, lymphoplasmacytic inflammation, and fibrosis, a small foci of papillary renal cell carcinoma (PRCC) was identified, accounting for 75%. The remaining previously observed liver lesions were no longer visible (Fig. 2 bottom panel). The patient was asymptomatic, and the decision was made to continue with a period of observation, given the dramatic resolution of the multiple hepatic and pulmonary lesions after resection of the primary mass and retroperitoneal adenopathy.
DISCUSSION BY PETER VAN VELDHUIZEN, M.D. Renal cell carcinoma accounts for 3.9% of all new cancer diagnoses.1 There is estimated to be 64,000 newly 284
diagnosed cases of renal cell cancer in 2014.1 Of all renal tumors, 85% are clear cell histology. The remaining histologies are divided between papillary (10%-15%), chromophobe (4%-5%), and collecting duct tumors.2 Most recommendations originate from the treatment of clear cell carcinoma. It is unclear if current treatment strategies for clear cell renal carcinoma translate into optimal treatment for noneclear cell histologies. As such, enrollment in a clinical trial is recommended. Several such ongoing clinical trials for PRCC using agents targeted to block the MET pathway that has been shown to be upregulated in PRCC.3 Spontaneous regression of distant metastatic disease after debulking nephrectomy is a phenomenon that has been described in the literature since 1928 by Bumpus.4 Spontaneous regression of metastatic carcinoma has been defined as the disappearance of a metastatic lesion with therapy that is typically considered to be inadequate to exert such a significant response.5 The true incidence of spontaneous regression is unknown but most likely occurs in 20, although not all visualized on these images) low-signal hepatic lesions. Target lesions in segments 2 and 7 (top left and right, respectively) are marked with arrows. Bottom row: T1 postcontrast images from the postoperative magnetic resonance imaging show that all but 2 of the hepatic lesions have resolved. The target lesions have decreased significantly in size, with the segment 2 lesion (bottom left) now measuring 0.4 cm, previously 1.1 cm. The segment 7 lesion (bottom right) now measures 0.5 cm, previously 1.2 cm. (Color version available online.)
Figure 3. Preoperative magnetic resonance showing multiple small lung lesions.
imaging
Tumor-infiltrating lymphocytes (TILs) have been shown to have a role in the balance of the immune system’s regulation of malignancy and have been harvested in other malignancies such as melanoma. These TILs have been used in conjunction with interleukin-2 for autologous immunotherapy.13 The primary tumor in our patient’s case UROLOGY 85 (2), 2015
measured 15 cm, but
CASE PRESENTATION
A
previously healthy 69-year-old woman sought medical attention for stomach pain and distension associated with a 10-pound weight loss. There was no hematuria, fevers, chills, night sweats, or fatigue. Past medical history was significant for hypertension. In 1989, she required a temporary colostomy after a partial colectomy secondary to a colonic perforation. Family history was significant for a brother with glioblastoma multiforme, and her mother had kidney disease of unknown etiology. She did not report any previous chemical exposure but is a current smoker with a 45-pack year history of tobacco abuse. Initial kidney, ureter, and bladder imaging was done and suggested constipation. Pain control was achieved with an aggressive bowel regimen and pain medication, but the sensation of abdominal fullness persisted. On presentation to our clinic, vital signs were normal except for a 10-pound weight loss over a 3-week period. Physical examination revealed a left large, palpable, flank mass that was tender to palpation but no other palpable adenopathy. Her initial laboratory evaluation was significant for hemoglobin 10.3 g/dL, creatinine 1.17 mg/dL, calcium 10.0 mg/dL, albumin 4.0 g/dL, and lactate dehydrogenase 543 U/L (100-210 U/L). A computed tomography scan of the abdomen and pelvis followed by magnetic resonance imaging (MRI) of the abdomen revealed a 13.6 11.6 9.9 cm heterogeneous left renal mass (Fig. 1) with bulky retroperitoneal lymphadenopathy, left renal vein thrombus, a nonocclusive inferior vena caval tumor thrombus, ipsilateral adrenal gland Rashna Madan provided the pathologic description and pathology images for this case. Peter Van Veldhuizen is the senior author of this article and provided the discussion. Aaron Kovaleski provided the radiographic images and description, and Travis Williams, Robert Rodriguez, and Katie Murray were responsible for the remainder of the article. Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Hematology/Oncology, University of Kansas Medical Center, Kansas City, KS; the Department of Urology, University of Kansas Medical Center, Kansas City, KS; the Department of Radiology, University of Kansas Medical Center, Kansas City, KS; and the Department of Pathology, University of Kansas Medical Center, Kansas City, KS Address correspondence to: Travis Williams, D.O., Department of Hematology/ Oncology, University of Kansas Medical Center, 2330 Shawnee Mission Parkway Suite 210, Westwood, KS 66205. E-mail: [email protected] Submitted: May 12, 2014, accepted (with revisions): October 4, 2014
ª 2015 Elsevier Inc. All Rights Reserved
involvement, and innumerable hepatic and pulmonary metastasis measuring 5-10 and 3-5 mm, respectively (Figs. 2, 3). There was no evidence of cerebral or osseous metastasis on imaging studies.
DIFFERENTIAL DIAGNOSIS Several conditions were initially considered in the differential diagnosis. The imaging studies revealed metastatic disease involving lung, liver, kidney, and retroperitoneal adenopathy. Clear cell renal cell carcinoma was a consideration, given the large size of the left renal mass and inferior vena caval tumor thrombus. Metastatic carcinoma of likely ovarian or colonic origin was also considered. A concerning historical component was that her mother had been on dialysis for unexplained causes. Concern for an inherited familial renal malignancy such as von Hippel-Lindau syndrome, hereditary leiomyomatosis-associated renal cell cancer, Birt-Hogg-Dube syndrome, and hereditary papillary renal cancer were considered but felt unlikely given the patient’s age and lack of strong family history for malignancy.
MANAGEMENT AND OUTCOME She was referred for a palliative debulking nephrectomy, believing that her pain was secondary to the large left renal mass palpated on examination. The surgical procedures performed included left radical nephrectomy, retroperitoneal lymph node dissection, caval thrombectomy, splenectomy, and extensive lysis of adhesions. The nephrectomy revealed a 15.5 9.5 8.0 cm predominantly necrotic mass that obliterated the renal parenchyma and extended into the renal vein. Although the bulk of the tumor was necrotic with accompanying foamy macrophages, lymphoplasmacytic inflammation, and fibrosis, a small foci of papillary renal cell carcinoma (PRCC) was identified, accounting for 75%. The remaining previously observed liver lesions were no longer visible (Fig. 2 bottom panel). The patient was asymptomatic, and the decision was made to continue with a period of observation, given the dramatic resolution of the multiple hepatic and pulmonary lesions after resection of the primary mass and retroperitoneal adenopathy.
DISCUSSION BY PETER VAN VELDHUIZEN, M.D. Renal cell carcinoma accounts for 3.9% of all new cancer diagnoses.1 There is estimated to be 64,000 newly 284
diagnosed cases of renal cell cancer in 2014.1 Of all renal tumors, 85% are clear cell histology. The remaining histologies are divided between papillary (10%-15%), chromophobe (4%-5%), and collecting duct tumors.2 Most recommendations originate from the treatment of clear cell carcinoma. It is unclear if current treatment strategies for clear cell renal carcinoma translate into optimal treatment for noneclear cell histologies. As such, enrollment in a clinical trial is recommended. Several such ongoing clinical trials for PRCC using agents targeted to block the MET pathway that has been shown to be upregulated in PRCC.3 Spontaneous regression of distant metastatic disease after debulking nephrectomy is a phenomenon that has been described in the literature since 1928 by Bumpus.4 Spontaneous regression of metastatic carcinoma has been defined as the disappearance of a metastatic lesion with therapy that is typically considered to be inadequate to exert such a significant response.5 The true incidence of spontaneous regression is unknown but most likely occurs in 20, although not all visualized on these images) low-signal hepatic lesions. Target lesions in segments 2 and 7 (top left and right, respectively) are marked with arrows. Bottom row: T1 postcontrast images from the postoperative magnetic resonance imaging show that all but 2 of the hepatic lesions have resolved. The target lesions have decreased significantly in size, with the segment 2 lesion (bottom left) now measuring 0.4 cm, previously 1.1 cm. The segment 7 lesion (bottom right) now measures 0.5 cm, previously 1.2 cm. (Color version available online.)
Figure 3. Preoperative magnetic resonance showing multiple small lung lesions.
imaging
Tumor-infiltrating lymphocytes (TILs) have been shown to have a role in the balance of the immune system’s regulation of malignancy and have been harvested in other malignancies such as melanoma. These TILs have been used in conjunction with interleukin-2 for autologous immunotherapy.13 The primary tumor in our patient’s case UROLOGY 85 (2), 2015
measured 15 cm, but
