Accepted Manuscript Spontaneous Tumor Lysis Syndrome in Renal Cell Carcinoma - A Case Report Norberg SM, D.O Oros M, D.O Birkenbach M, M.D. Bilusic M, M.D, PhD PII:
S1558-7673(14)00112-8
DOI:
10.1016/j.clgc.2014.04.007
Reference:
CLGC 282
To appear in:
Clinical Genitourinary Cancer
Received Date: 28 February 2014 Revised Date:
11 April 2014
Accepted Date: 23 April 2014
Please cite this article as: SM N, M O, M B, M B, Spontaneous Tumor Lysis Syndrome in Renal Cell Carcinoma - A Case Report, Clinical Genitourinary Cancer (2014), doi: 10.1016/j.clgc.2014.04.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Spontaneous Tumor Lysis Syndrome in Renal Cell Carcinoma - A Case Report Norberg SM1 D.O, Oros M1 D.O, Birkenbach M1 M.D., and Bilusic M2 M.D, PhD. 1
Temple University Hospital
RI PT
3401 N Broad St Philadelphia, PA 19140 Fax# 215-707-5978 2
Fox Chase Cancer Center 333 Cottman Avenue
Fax# 215-728-3639
SC
Philadelphia, PA 19111-2497
M AN U
Scott M. Norberg – [email protected], Michelle Oros - [email protected], Mark Birkenbach - [email protected], *Marijo Bilusic - [email protected] *Corresponding Author Number of words: 1,270
TE D
Clinical Practice Points:
Spontaneous tumor lysis syndrome (STLS) is a rare oncologic emergency caused by acute and massive death of tumor cells prior to the initiation of any anti-cancer therapy. It is commonly associated with aggressive hematological malignancies; however, it has been more
EP
frequently recognized in multiple solid tumors. Our literature search of STLS in solid tumors revealed common characteristics including extensive metastatic disease and elevated levels of
AC C
uric acid and lactate dehydrogenase (LDH). In this report, we describe, to our knowledge, the first case of STLS caused by a renal cell carcinoma and discuss the need for developing screening guidelines for this deadly syndrome.
Introduction:
Tumor lysis syndrome (TLS) is a condition that may occur following the treatment of a malignancy. It results from the rapid necrosis of tumor cells resulting in multiple metabolic abnormalities (hyperphosphatemia, hypocalcemia, hyperkalemia and hyperuricemia) and
ACCEPTED MANUSCRIPT
clinical complications; however, it can also occur spontaneously and should be timely recognized and aggressively treated. The most commonly used classification for TLS, the CairoBishop definition, was proposed in 2004 [1]. At least two laboratory criteria must be present for three days before treatment or up to seven days after treatment (Table 1).
RI PT
Spontaneous tumor lysis syndrome (STLS) has been well documented and recognized in multiple hematologic malignancies, mostly in aggressive non-Hodgkin lymphomas and acute leukemias [2-4]. The incidence of STLS in patients with solid tumors is unknown, but it is believed to be extremely rare. Our search of Pubmed database for STLS in solid tumors
SC
revealed less than 20 case reports, most of which have been reported within the past 10 years. We were not able to find any case report of STLS in metastatic kidney cancer.
M AN U
Renal cell carcinoma is considered to be a relatively common malignancy with incidence varying greatly between races, sexes, geographic location and ages. In the United States alone, there is an average of 64,000 new cases diagnosed each year [5]. It is the most common type of kidney cancer in adults, responsible for approximately 90-95% of cases [6]. In this article, we discuss the first ever reported case of STLS due to a renal cell carcinoma. Our patient was a 56-year old Caucasian man with a past medical history of
TE D
hypertension who was in his usual state of health when he presented to his local hospital with hematuria. Initial work-up was non-conclusive including normal blood work, negative cystoscopy and urine cytology. Due to persistent hematuria, a repeated cystouretheroscopy was performed. A biopsy revealed a noninvasive low-grade papillary urothelial neoplasm. He underwent a renal
EP
scan that revealed a large left mid-to-lower pole defect. While awaiting therapeutic nephrectomy, our patient began to develop severe back pain. A MRI of the spine showed a pathologic compression fracture at T11 and metastatic disease at T6, T8 and T9 vertebra. A CT
AC C
urogram showed multiple hypodense lesions in the liver. Ultrasound guided liver biopsy was performed and results were not conclusive; therefore, the pathology slides were sent for a second opinion.
While waiting for the final diagnosis, the patient presented to us with severe back pain, night
sweats,
weight
loss
and
low-grade
fevers.
His
medications
included
lisinopril/hydrochlorothiazide, ciprofloxacin, percocet and fentanyl. Physical examination revealed normal vitals, jaundice and ascites with 10 cm palpable liver below the costal margin. The rest of the examination was unremarkable. CT scan demonstrated extensive metastatic abdominal lymphadenopathy, multiple liver lesions and a mass expanding the left renal sinus
ACCEPTED MANUSCRIPT
(Figure 1). CBC revealed WBC count of 20.5 K/mm3, hemoglobin of 16.5 gm/dL, platelet count of 487,000 K/mm3. Other pertinent laboratory studies included a potassium of 5.0 mmol/L, calcium 9.4 mg/dL, BUN 66 mg/dL, creatinine 3.98 mg/dL, LDH 2373 units/L, phosphorus 10.5 mg/dL and uric acid 24.6 mg/dL. His previous blood work from one month prior was
RI PT
unremarkable. He was admitted to the ICU for the management of STLS and multi-organ failure. He endured a complicated ICU course and eventually developed septic shock. The decision was made not to treat the patient with chemotherapy given his critical condition. His condition
SC
deteriorated rapidly and he expired 1 week later. Post-mortem examination revealed a dominant tumor mass in the upper pole and mid-portion of the left kidney measuring 10 x 6.5 x 6.2 cm. The tumor extended to the renal capsule and left renal sinus. Cut-section demonstrated a
M AN U
variegated appearance with predominantly yellow coloration and extensive areas of hemorrhage and necrosis (Figure 2A). Light microscopy revealed a poorly differentiated carcinoma composed
of
medium-sized
cells,
hyperchromatic
nuclei
and
clear
cytoplasm.
Immunohistochemical stains were positive for vimentin and CD10 and negative for a broad range of cytokerantins and markers of neuroendocrine, melanocytic, hepatocyte and hematopoietic differentiation. Gross and microscopic features were consistent with poorly
TE D
differentiated renal cell carcinoma. (Figure 2B) Metastatic disease was found in adrenal glands, mesentery, liver, pleura, left bronchus, lumbar spine and lymph nodes. His initial liver biopsy
Discussion:
EP
ended up showing a high grade, poorly differentiated tumor that stained weakly for PAX-8.
AC C
Our patient was relatively asymptomatic at presentation; however he met the clinical diagnosis of tumor lysis syndrome (one clinical symptom in addition to two laboratory criteria) based on his acute renal failure, hyperphosphatemia and hyperuricemia. His diagnosis was recognized very quickly and he was treated with appropriate supportive measures including aggressive IV hydration, allopurinol and hemodialysis. Unfortunately, due to extensive metastatic disease, he developed irreversible multi-organ system failure and expired several days later. Autopsy revealed extensive areas of hemorrhage and necrosis, which supported our initial clinical diagnosis.
ACCEPTED MANUSCRIPT
STLS is not as common in solid tumors, but we believe that it might be underdiagnosed, as many milder cases could be missed easily without a high index of suspicion. STLS has been reported in gastric cancer [7], lung [8], pheochromocytoma [9], breast [10], hepatocellular cancer [11], melanoma [12], sarcoma [13] and adenocarcinoma of unknown primary [14]. There
RI PT
are five case reports of STLS in genitourinary cancers: four in germ cell tumors [15-17] and one in prostate carcinoma [18]. No cases have been described in renal cell carcinoma. In reported cases of STLS, the median LDH was 1,276.5 IU/mL (range 509 to 13,924), median uric acid was 20.25 mg/dL (range 10.1-37), median phosphorus 7.15 mg/dL (range 3.3 to 11.8), median creatinine 3.8 mg/dL (range 0.9 to 6.4), median potassium 6.5 mg/dL (range 4.5 to 8.5), and
the cases revealed extensive necrotic tissue in the tumor.
SC
median calcium 7.6 mg/dL (range 5 to 10.1). The biopsy and/or autopsy in the vast majority of
M AN U
A large primary tumor with significant liver and bone metastases, the presence of largesized masses, lymph node involvement, elevated uric acid and LDH levels may determine patients who are at risk for developing STLS or TLS once treatment is initiated. Liver and bone metastasis may undergo rapid central necrosis due to increased interstitial pressure, insufficient perfusion and hypoxemia. Using uric acid and LDH as a screening test in patients with extensive metastatic disease may help identify asymptomatic STLS. If the patient has additional
TE D
risk factors such as chronic renal insufficiency, volume contraction or hypotension, the patient may potentially be at very high risk for this syndrome. As more cases of STLS in solid tumors
Conclusion:
EP
are reported, the development of a risk stratification guideline becomes more essential.
AC C
STLS is a medical emergency that has become more frequently reported as a complication of solid tumors. The current risk stratification guidelines do not address prophylaxis in either hematologic or non-hematologic tumors susceptible to developing STLS. Screening with uric acid and LDH in patients with highly aggressive malignancies could help identify those that would benefit from prophylactic treatments. STLS should be entertained in the differential diagnosis of patients with advanced malignancy and kidney injury in the setting of characteristic laboratory abnormalities.
Consent:
ACCEPTED MANUSCRIPT
Verbal consent was obtained from the patient’s wife and son.
List of abbreviations used:
RI PT
Spontaneous Tumor Lysis Syndrome (STLS), Tumor Lysis Syndrome (TLS), Lactate Dehydrogenase (LDH), Intravenous (IV)
SC
Competing Interests:
M AN U
None
Authors’ Contributions:
Scott Norberg and Marijo Bilusic researched the current literature and wrote the case report except for the pathology portion. Michelle Oros and Mark Birkenbach performed the postmortem examination, interpreted results and provided the images used in the case report. All
AC C
EP
TE D
authors read and approved the final manuscript.
ACCEPTED MANUSCRIPT
REFERENCES:
7.
8. 9.
10. 11. 12. 13. 14.
15.
16.
17.
18.
RI PT
SC
5. 6.
M AN U
4.
TE D
3.
EP
2.
Cairo MS, Bishop M: Tumour lysis syndrome: new therapeutic strategies and classification. British journal of haematology 2004, 127:3-11. Hande KR, Garrow GC: Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma. The American journal of medicine 1993, 94:133-139. Jasek AM, Day HJ: Acute spontaneous tumor lysis syndrome. American journal of hematology 1994, 47:129-131. Tsokos GC, Balow JE, Spiegel RJ, Magrath IT: Renal and metabolic complications of undifferentiated and lymphoblastic lymphomas. Medicine 1981, 60:218-229. Siegel R, Ma J, Zou Z, Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9 Curti, B; Jana, BRP; Javeed, M; Makhoul, I; Sachdeva, K; Hu, W; Perry, M; Talavera, F: Renal Cell Carcinoma. In Harris, JE. Medscape Reference. Woo IS, Kim JS, Park MJ, Lee MS, Cheon RW, Chang HM, Ahn JS, Lee JA, Park YI, Park YS, et al: Spontaneous acute tumor lysis syndrome with advanced gastric cancer. Journal of Korean medical science 2001, 16:115-118. Feld J, Mehta H, Burkes RL: Acute spontaneous tumor lysis syndrome in adenocarcinoma of the lung: a case report. American journal of clinical oncology 2000, 23:491-493. Vaisban E, Braester A, Mosenzon O, Kolin M, Horn Y: Spontaneous tumor lysis syndrome in solid tumors: really a rare condition? The American journal of the medical sciences 2003, 325:38-40. Sklarin NT, Markham M: Spontaneous recurrent tumor lysis syndrome in breast cancer. American journal of clinical oncology 1995, 18:71-73. Kekre N, Djordjevic B, Touchie C: Spontaneous tumour lysis syndrome. Canadian Medical Association Journal 2012, 184:913-916. Mouallem M, Zemer-Wassercug N, Kugler E, Sahar N, Shapira-Frommer R, Schiby G: Tumor lysis syndrome and malignant melanoma. Medical oncology 2013, 30:364. Baeksgaard L, Sorensen JB: Acute tumor lysis syndrome in solid tumors--a case report and review of the literature. Cancer chemotherapy and pharmacology 2003, 51:187-192. Saini N, Pyo Lee K, Jha S, Patel S, Bonthu N, Kansagra A, Bhatia A, Martinez SE, Patel J, Altamimi S, Ghotb S: Hyperuricemic renal failure in nonhematologic solid tumors: a case report and review of the literature. Case reports in medicine 2012, 2012:314056. D'Alessandro V, Greco A, Clemente C, Sperandeo M, De Cata A, Di Micco C, Maiello E, Vendemiale G: Severe spontaneous acute tumor lysis syndrome and hypoglycemia in patient with germ cell tumor. Tumori 2010, 96:1040-1043. Murray MJ, Metayer LE, Mallucci CL, Hale JP, Nicholson JC, Kirollos RW, Burke GA: Intraabdominal metastasis of an intracranial germinoma via ventriculo-peritoneal shunt in a 13year-old female. British journal of neurosurgery 2011, 25:747-749. Pentheroudakis G, O'Neill VJ, Vasey P, Kaye SB: Spontaneous acute tumour lysis syndrome in patients with metastatic germ cell tumours. Report of two cases. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2001, 9:554-557. Lin CJ, Hsieh RK, Lim KH, Chen HH, Cheng YC, Wu CJ: Fatal spontaneous tumor lysis syndrome in a patient with metastatic, androgen-independent prostate cancer. Southern medical journal 2007, 100:916-917.
AC C
1.
ACCEPTED MANUSCRIPT
Figure Legends:
RI PT
Figure 1. CT Scan showing tumor and adenopathy. CT imaging demonstrates tumor expanding the left renal sinus and left retroperitoneal metastatic adenopathy.
SC
Figure 2A. Cut section showing predominant tumor mass with extensive necrosis. Gross tissue sectioning shows a predominant tumor mass with extensive involvement of left kidney upper pole and mid-portion along with extensive replacement of renal sinus adipose tissue. Extensive areas of necrosis are grossly evident throughout the tumor.
AC C
EP
TE D
M AN U
Figure 2B. Microscopic imaging showing malignant cells. Microscopic appearance of renal tumor shows a relatively uniform population of cytologically malignant cells with clear cytoplasm. Most of the tumor examined microscopically was necrotic (not shown).
ACCEPTED MANUSCRIPT
Table 1: The Cairo-Bishop classification system for tumor lysis syndrome Laboratory criteria Value
% change from baseline
Uric Acid
≥ 476 µmol/L (8 mg/dL)
25% increase
Potassium
≥ 6.0 mmol/L (6 mEq/L)
25% increase
Phosphorus
≥ 1.45 mmol/L (4.5 mg/dL) - adults
Calcium
≥ 1.75 mmol/L (7 mg/dL)
SC
RI PT
Lab Study
25% increase
M AN U
25% decrease
Clinical criteria
AC C
EP
TE D
1. Creatinine ≥ 1.5 times the Upper limit of normal (age >12 years or age adjusted) 2. Cardiac arrhythmia or sudden death 3. Seizure
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S1558-7673(14)00112-8
DOI:
10.1016/j.clgc.2014.04.007
Reference:
CLGC 282
To appear in:
Clinical Genitourinary Cancer
Received Date: 28 February 2014 Revised Date:
11 April 2014
Accepted Date: 23 April 2014
Please cite this article as: SM N, M O, M B, M B, Spontaneous Tumor Lysis Syndrome in Renal Cell Carcinoma - A Case Report, Clinical Genitourinary Cancer (2014), doi: 10.1016/j.clgc.2014.04.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Spontaneous Tumor Lysis Syndrome in Renal Cell Carcinoma - A Case Report Norberg SM1 D.O, Oros M1 D.O, Birkenbach M1 M.D., and Bilusic M2 M.D, PhD. 1
Temple University Hospital
RI PT
3401 N Broad St Philadelphia, PA 19140 Fax# 215-707-5978 2
Fox Chase Cancer Center 333 Cottman Avenue
Fax# 215-728-3639
SC
Philadelphia, PA 19111-2497
M AN U
Scott M. Norberg – [email protected], Michelle Oros - [email protected], Mark Birkenbach - [email protected], *Marijo Bilusic - [email protected] *Corresponding Author Number of words: 1,270
TE D
Clinical Practice Points:
Spontaneous tumor lysis syndrome (STLS) is a rare oncologic emergency caused by acute and massive death of tumor cells prior to the initiation of any anti-cancer therapy. It is commonly associated with aggressive hematological malignancies; however, it has been more
EP
frequently recognized in multiple solid tumors. Our literature search of STLS in solid tumors revealed common characteristics including extensive metastatic disease and elevated levels of
AC C
uric acid and lactate dehydrogenase (LDH). In this report, we describe, to our knowledge, the first case of STLS caused by a renal cell carcinoma and discuss the need for developing screening guidelines for this deadly syndrome.
Introduction:
Tumor lysis syndrome (TLS) is a condition that may occur following the treatment of a malignancy. It results from the rapid necrosis of tumor cells resulting in multiple metabolic abnormalities (hyperphosphatemia, hypocalcemia, hyperkalemia and hyperuricemia) and
ACCEPTED MANUSCRIPT
clinical complications; however, it can also occur spontaneously and should be timely recognized and aggressively treated. The most commonly used classification for TLS, the CairoBishop definition, was proposed in 2004 [1]. At least two laboratory criteria must be present for three days before treatment or up to seven days after treatment (Table 1).
RI PT
Spontaneous tumor lysis syndrome (STLS) has been well documented and recognized in multiple hematologic malignancies, mostly in aggressive non-Hodgkin lymphomas and acute leukemias [2-4]. The incidence of STLS in patients with solid tumors is unknown, but it is believed to be extremely rare. Our search of Pubmed database for STLS in solid tumors
SC
revealed less than 20 case reports, most of which have been reported within the past 10 years. We were not able to find any case report of STLS in metastatic kidney cancer.
M AN U
Renal cell carcinoma is considered to be a relatively common malignancy with incidence varying greatly between races, sexes, geographic location and ages. In the United States alone, there is an average of 64,000 new cases diagnosed each year [5]. It is the most common type of kidney cancer in adults, responsible for approximately 90-95% of cases [6]. In this article, we discuss the first ever reported case of STLS due to a renal cell carcinoma. Our patient was a 56-year old Caucasian man with a past medical history of
TE D
hypertension who was in his usual state of health when he presented to his local hospital with hematuria. Initial work-up was non-conclusive including normal blood work, negative cystoscopy and urine cytology. Due to persistent hematuria, a repeated cystouretheroscopy was performed. A biopsy revealed a noninvasive low-grade papillary urothelial neoplasm. He underwent a renal
EP
scan that revealed a large left mid-to-lower pole defect. While awaiting therapeutic nephrectomy, our patient began to develop severe back pain. A MRI of the spine showed a pathologic compression fracture at T11 and metastatic disease at T6, T8 and T9 vertebra. A CT
AC C
urogram showed multiple hypodense lesions in the liver. Ultrasound guided liver biopsy was performed and results were not conclusive; therefore, the pathology slides were sent for a second opinion.
While waiting for the final diagnosis, the patient presented to us with severe back pain, night
sweats,
weight
loss
and
low-grade
fevers.
His
medications
included
lisinopril/hydrochlorothiazide, ciprofloxacin, percocet and fentanyl. Physical examination revealed normal vitals, jaundice and ascites with 10 cm palpable liver below the costal margin. The rest of the examination was unremarkable. CT scan demonstrated extensive metastatic abdominal lymphadenopathy, multiple liver lesions and a mass expanding the left renal sinus
ACCEPTED MANUSCRIPT
(Figure 1). CBC revealed WBC count of 20.5 K/mm3, hemoglobin of 16.5 gm/dL, platelet count of 487,000 K/mm3. Other pertinent laboratory studies included a potassium of 5.0 mmol/L, calcium 9.4 mg/dL, BUN 66 mg/dL, creatinine 3.98 mg/dL, LDH 2373 units/L, phosphorus 10.5 mg/dL and uric acid 24.6 mg/dL. His previous blood work from one month prior was
RI PT
unremarkable. He was admitted to the ICU for the management of STLS and multi-organ failure. He endured a complicated ICU course and eventually developed septic shock. The decision was made not to treat the patient with chemotherapy given his critical condition. His condition
SC
deteriorated rapidly and he expired 1 week later. Post-mortem examination revealed a dominant tumor mass in the upper pole and mid-portion of the left kidney measuring 10 x 6.5 x 6.2 cm. The tumor extended to the renal capsule and left renal sinus. Cut-section demonstrated a
M AN U
variegated appearance with predominantly yellow coloration and extensive areas of hemorrhage and necrosis (Figure 2A). Light microscopy revealed a poorly differentiated carcinoma composed
of
medium-sized
cells,
hyperchromatic
nuclei
and
clear
cytoplasm.
Immunohistochemical stains were positive for vimentin and CD10 and negative for a broad range of cytokerantins and markers of neuroendocrine, melanocytic, hepatocyte and hematopoietic differentiation. Gross and microscopic features were consistent with poorly
TE D
differentiated renal cell carcinoma. (Figure 2B) Metastatic disease was found in adrenal glands, mesentery, liver, pleura, left bronchus, lumbar spine and lymph nodes. His initial liver biopsy
Discussion:
EP
ended up showing a high grade, poorly differentiated tumor that stained weakly for PAX-8.
AC C
Our patient was relatively asymptomatic at presentation; however he met the clinical diagnosis of tumor lysis syndrome (one clinical symptom in addition to two laboratory criteria) based on his acute renal failure, hyperphosphatemia and hyperuricemia. His diagnosis was recognized very quickly and he was treated with appropriate supportive measures including aggressive IV hydration, allopurinol and hemodialysis. Unfortunately, due to extensive metastatic disease, he developed irreversible multi-organ system failure and expired several days later. Autopsy revealed extensive areas of hemorrhage and necrosis, which supported our initial clinical diagnosis.
ACCEPTED MANUSCRIPT
STLS is not as common in solid tumors, but we believe that it might be underdiagnosed, as many milder cases could be missed easily without a high index of suspicion. STLS has been reported in gastric cancer [7], lung [8], pheochromocytoma [9], breast [10], hepatocellular cancer [11], melanoma [12], sarcoma [13] and adenocarcinoma of unknown primary [14]. There
RI PT
are five case reports of STLS in genitourinary cancers: four in germ cell tumors [15-17] and one in prostate carcinoma [18]. No cases have been described in renal cell carcinoma. In reported cases of STLS, the median LDH was 1,276.5 IU/mL (range 509 to 13,924), median uric acid was 20.25 mg/dL (range 10.1-37), median phosphorus 7.15 mg/dL (range 3.3 to 11.8), median creatinine 3.8 mg/dL (range 0.9 to 6.4), median potassium 6.5 mg/dL (range 4.5 to 8.5), and
the cases revealed extensive necrotic tissue in the tumor.
SC
median calcium 7.6 mg/dL (range 5 to 10.1). The biopsy and/or autopsy in the vast majority of
M AN U
A large primary tumor with significant liver and bone metastases, the presence of largesized masses, lymph node involvement, elevated uric acid and LDH levels may determine patients who are at risk for developing STLS or TLS once treatment is initiated. Liver and bone metastasis may undergo rapid central necrosis due to increased interstitial pressure, insufficient perfusion and hypoxemia. Using uric acid and LDH as a screening test in patients with extensive metastatic disease may help identify asymptomatic STLS. If the patient has additional
TE D
risk factors such as chronic renal insufficiency, volume contraction or hypotension, the patient may potentially be at very high risk for this syndrome. As more cases of STLS in solid tumors
Conclusion:
EP
are reported, the development of a risk stratification guideline becomes more essential.
AC C
STLS is a medical emergency that has become more frequently reported as a complication of solid tumors. The current risk stratification guidelines do not address prophylaxis in either hematologic or non-hematologic tumors susceptible to developing STLS. Screening with uric acid and LDH in patients with highly aggressive malignancies could help identify those that would benefit from prophylactic treatments. STLS should be entertained in the differential diagnosis of patients with advanced malignancy and kidney injury in the setting of characteristic laboratory abnormalities.
Consent:
ACCEPTED MANUSCRIPT
Verbal consent was obtained from the patient’s wife and son.
List of abbreviations used:
RI PT
Spontaneous Tumor Lysis Syndrome (STLS), Tumor Lysis Syndrome (TLS), Lactate Dehydrogenase (LDH), Intravenous (IV)
SC
Competing Interests:
M AN U
None
Authors’ Contributions:
Scott Norberg and Marijo Bilusic researched the current literature and wrote the case report except for the pathology portion. Michelle Oros and Mark Birkenbach performed the postmortem examination, interpreted results and provided the images used in the case report. All
AC C
EP
TE D
authors read and approved the final manuscript.
ACCEPTED MANUSCRIPT
REFERENCES:
7.
8. 9.
10. 11. 12. 13. 14.
15.
16.
17.
18.
RI PT
SC
5. 6.
M AN U
4.
TE D
3.
EP
2.
Cairo MS, Bishop M: Tumour lysis syndrome: new therapeutic strategies and classification. British journal of haematology 2004, 127:3-11. Hande KR, Garrow GC: Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma. The American journal of medicine 1993, 94:133-139. Jasek AM, Day HJ: Acute spontaneous tumor lysis syndrome. American journal of hematology 1994, 47:129-131. Tsokos GC, Balow JE, Spiegel RJ, Magrath IT: Renal and metabolic complications of undifferentiated and lymphoblastic lymphomas. Medicine 1981, 60:218-229. Siegel R, Ma J, Zou Z, Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9 Curti, B; Jana, BRP; Javeed, M; Makhoul, I; Sachdeva, K; Hu, W; Perry, M; Talavera, F: Renal Cell Carcinoma. In Harris, JE. Medscape Reference. Woo IS, Kim JS, Park MJ, Lee MS, Cheon RW, Chang HM, Ahn JS, Lee JA, Park YI, Park YS, et al: Spontaneous acute tumor lysis syndrome with advanced gastric cancer. Journal of Korean medical science 2001, 16:115-118. Feld J, Mehta H, Burkes RL: Acute spontaneous tumor lysis syndrome in adenocarcinoma of the lung: a case report. American journal of clinical oncology 2000, 23:491-493. Vaisban E, Braester A, Mosenzon O, Kolin M, Horn Y: Spontaneous tumor lysis syndrome in solid tumors: really a rare condition? The American journal of the medical sciences 2003, 325:38-40. Sklarin NT, Markham M: Spontaneous recurrent tumor lysis syndrome in breast cancer. American journal of clinical oncology 1995, 18:71-73. Kekre N, Djordjevic B, Touchie C: Spontaneous tumour lysis syndrome. Canadian Medical Association Journal 2012, 184:913-916. Mouallem M, Zemer-Wassercug N, Kugler E, Sahar N, Shapira-Frommer R, Schiby G: Tumor lysis syndrome and malignant melanoma. Medical oncology 2013, 30:364. Baeksgaard L, Sorensen JB: Acute tumor lysis syndrome in solid tumors--a case report and review of the literature. Cancer chemotherapy and pharmacology 2003, 51:187-192. Saini N, Pyo Lee K, Jha S, Patel S, Bonthu N, Kansagra A, Bhatia A, Martinez SE, Patel J, Altamimi S, Ghotb S: Hyperuricemic renal failure in nonhematologic solid tumors: a case report and review of the literature. Case reports in medicine 2012, 2012:314056. D'Alessandro V, Greco A, Clemente C, Sperandeo M, De Cata A, Di Micco C, Maiello E, Vendemiale G: Severe spontaneous acute tumor lysis syndrome and hypoglycemia in patient with germ cell tumor. Tumori 2010, 96:1040-1043. Murray MJ, Metayer LE, Mallucci CL, Hale JP, Nicholson JC, Kirollos RW, Burke GA: Intraabdominal metastasis of an intracranial germinoma via ventriculo-peritoneal shunt in a 13year-old female. British journal of neurosurgery 2011, 25:747-749. Pentheroudakis G, O'Neill VJ, Vasey P, Kaye SB: Spontaneous acute tumour lysis syndrome in patients with metastatic germ cell tumours. Report of two cases. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2001, 9:554-557. Lin CJ, Hsieh RK, Lim KH, Chen HH, Cheng YC, Wu CJ: Fatal spontaneous tumor lysis syndrome in a patient with metastatic, androgen-independent prostate cancer. Southern medical journal 2007, 100:916-917.
AC C
1.
ACCEPTED MANUSCRIPT
Figure Legends:
RI PT
Figure 1. CT Scan showing tumor and adenopathy. CT imaging demonstrates tumor expanding the left renal sinus and left retroperitoneal metastatic adenopathy.
SC
Figure 2A. Cut section showing predominant tumor mass with extensive necrosis. Gross tissue sectioning shows a predominant tumor mass with extensive involvement of left kidney upper pole and mid-portion along with extensive replacement of renal sinus adipose tissue. Extensive areas of necrosis are grossly evident throughout the tumor.
AC C
EP
TE D
M AN U
Figure 2B. Microscopic imaging showing malignant cells. Microscopic appearance of renal tumor shows a relatively uniform population of cytologically malignant cells with clear cytoplasm. Most of the tumor examined microscopically was necrotic (not shown).
ACCEPTED MANUSCRIPT
Table 1: The Cairo-Bishop classification system for tumor lysis syndrome Laboratory criteria Value
% change from baseline
Uric Acid
≥ 476 µmol/L (8 mg/dL)
25% increase
Potassium
≥ 6.0 mmol/L (6 mEq/L)
25% increase
Phosphorus
≥ 1.45 mmol/L (4.5 mg/dL) - adults
Calcium
≥ 1.75 mmol/L (7 mg/dL)
SC
RI PT
Lab Study
25% increase
M AN U
25% decrease
Clinical criteria
AC C
EP
TE D
1. Creatinine ≥ 1.5 times the Upper limit of normal (age >12 years or age adjusted) 2. Cardiac arrhythmia or sudden death 3. Seizure
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
