World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Case Report

Volume 6, Number 5, October 2015, pages 464-471

Spontaneous Tumor Lysis Syndrome in Small-Cell Lung Cancer: A Rare Complication

**Table 1.** Laboratory Values on Admission
Description	Results	Units	Reference range
Leukocyte count	12.23	× 10⁹/L	4.8 - 10.8
Hemoglobin	11.8	g/dL	14 - 18
Hematocrit	33.8	%	42 - 52
Platelets	405	× 10⁹/L	130 - 400
Sodium	131	mEq/L	135 - 146
Potassium	7.4	mEq/L	3.5 - 5
Chloride	101	mEq/L	98 - 110
Carbon dioxide	12	mEq/L	17-32
Anion gap	18	mEq/L	7-14
Glucose	136	mg/dL	70 - 110
Urea	66	mg/dL	10 - 20
Creatinine	3.92	mg/dL	0.7 - 1.5
Calcium	8.2	mg/dL	8.5 - 10.1
Inorganic phosphorus	4.3	mg/dL	2.1 - 4.9
Magnesium	2.3	mg/dL	1.8 - 2.4
Albumin	2.9	g/dL	3.0 - 5.5
Total bilirubin	5.9	mg/dL	0.2 - 1.2
Alanine aminotransferase	86	IU/L	0 - 45
Aspartate aminotransferase	92	IU/L	0 - 41
Alkaline phosphatase	498	IU/L	30 - 115
LDH	913	IU/L	60 - 200
Uric acid	16.5	mg/dL	4.8 - 8.7
Lactic acid	8.5	mmol/L	0.5 - 2.2

Table 1. Laboratory Values on Admission

Description

Results

Units

Reference range

Leukocyte count

12.23

× 10⁹/L

4.8 - 10.8

Hemoglobin

11.8

g/dL

14 - 18

Hematocrit

33.8

42 - 52

Platelets

405

× 10⁹/L

130 - 400

Sodium

131

mEq/L

135 - 146

Potassium

7.4

mEq/L

3.5 - 5

Chloride

101

mEq/L

98 - 110

Carbon dioxide

mEq/L

17-32

Anion gap

mEq/L

7-14

Glucose

136

mg/dL

70 - 110

Urea

mg/dL

10 - 20

Creatinine

3.92

mg/dL

0.7 - 1.5

Calcium

8.2

mg/dL

8.5 - 10.1

Inorganic phosphorus

4.3

mg/dL

2.1 - 4.9

Magnesium

2.3

mg/dL

1.8 - 2.4

Albumin

2.9

g/dL

3.0 - 5.5

Total bilirubin

5.9

mg/dL

0.2 - 1.2

Alanine aminotransferase

IU/L

0 - 45

Aspartate aminotransferase

IU/L

0 - 41

Alkaline phosphatase

498

IU/L

30 - 115

LDH

913

IU/L

60 - 200

Uric acid

16.5

mg/dL

4.8 - 8.7

Lactic acid

8.5

mmol/L

0.5 - 2.2

**Table 2.** Cases of STLS in Solid Tumors [9-31]
Primary site and type of cancer	Tumor burden	Treatment	Outcome of TLS treatment	Year of publication
Adenocarcinoma of unknown primary [14]	- Liver and bone metastases - Bulky lymph nodes	- Hydration - Allopurinol - Alkalization	Death	1977
Inflammatory breast cancer [15]	- Large mass - Metastases to liver, bone, lungs, bone marrow	- Chemotherapy - Allopurinol	Survival	1995
Lung Adenocarcinoma [16]	- Large mass - Liver metastases	- Hydration - Allopurinol - Potassium and phosphate binders	Death	2000
Gastric Adenocarcinoma [17]	- Large mass > 7 cm in diameter - Liver metastases - Multiple lymph nodes	- Hydration - Chemotherapy - Allopurinol - Alkalization - Hemodialysis	Death	2001
Testicular germ cell tumor [18]	Case 1: - Liver and lung metastases - Bulky lymph nodes Case 2: - 20 × 25 cm retroperitoneal mass	- Surgery - Chemotherapy - Hemodialysis	Survival	2001
Colon cancer [11]	Liver metastases with necrosis	- Hydration - Allopurinol - Alkalization	Survival	2003
Hepatocellular carcinoma [11]	Large liver lesion	- Hydration - Allopurinol - Alkalization	Death	2003
Pheochromocytoma [11]	Large mass (20 cm diameter) with central necrosis	- Hydration - Allopurinol - Alkalization	Survival	2003
Prostate Cancer [19]	Liver and bone metastases	- Hydration - Allopurinol - Hemodialysis	Death	2007
Squamous cell Lung Cancer [12]	Advanced stage (stage IV)	- Hydration - Hemodialysis - Allopurinol - Chemotherapy	Survival	2009
Maxillary sinus squamous cell carcinoma [20]	Liver metastases	- Hydration - Rasburicase - Allopurinol	Death	2009
Germ cell tumor [21]	- 14 cm Retroperitoneal mass - Liver and lung metastases	- Hydration - Rasburicase	Death	2010
Germ cell tumor [22]	20 × 17 × 13 cm pelvic mass	- Hydration - Rasburicase - Chemotherapy - Surgery	Survival	2011
Small-cell lung cancer [10]	- Poorly differentiated tumor - Liver metastases	None	Death	2011
Melanoma [23]	Extensive metastases (including liver and spleen)	- Hydration - Hemodialysis	Death	2011
Hepatocellular carcinoma [24]	19.2 × 11 × 8 cm liver mass with extensive necrosis	- Hydration - Allopurinol - Hemodialysis	Death	2012
Small-cell lung Cancer [9]	- 4 cm obstructive lung mass - Multiple liver metastases and extensive lymph nodes	Hydration	Death	2012
Adenocarcinoma of unknown primary [25]	- Liver metastases, possible lung and bone metastases - Bulky retroperitoneal mass 14 × 13 cm	- Hydration - Rasburicase - Hemodialysis	Death	2012
Melanoma [26]	Liver metastases	Hydration	Death	2013
Renal cell carcinoma [13]	- 10 × 6.5 × 6.2 cm renal mass with necrosis - Liver, bone, pleura, bronchus, adrenal glands metastases	- Hydration - Allopurinol - Hemodialysis	Death	2014
Cholangiocarcinoma [27]	Liver metastases	- Hydration - Allopurinol	Death	2014
Hepatocellular carcinoma [28]	- 14 × 14 cm liver mass -Multiple extensive lymph nodes	- Hydration - Alkalization	Unknown (hospice/palliative care)	2014
Gastric Adenocarcinoma [29]	- Liver, bone and adrenal gland metastases - Multiple lymph nodes	- Hydration - Allopurinol - Hemodialysis	Survival	2014
Skin Adenocarcinoma [30]	- Multiple subcutaneous, liver, kidney and adrenal gland metastasis	- Allopurinol - Potassium binders - Alkalinization	Death	2014
Pancreatic Adenocarcinoma [31]	- 6.7 × 10 cm mass - diffuse liver metastasis and extensive lymph nodes	- Hydration - Allopurinol - Rasburicase	Death	2015
Small-cell lung cancer (our case)	- Liver, bone metastasis - Extensive lymph nodes	- Hydration - Rasburicase - Allopurinol - Alkalization - Potassium binders - Chemotherapy	Survival	2015

Table 2. Cases of STLS in Solid Tumors [9-31]

Primary site and type of cancer

Tumor burden

Treatment

Outcome of TLS treatment

Year of publication

Adenocarcinoma of unknown primary [14]

- Liver and bone metastases
- Bulky lymph nodes

- Hydration
- Allopurinol
- Alkalization

Death

1977

Inflammatory breast cancer [15]

- Large mass
- Metastases to liver, bone, lungs, bone marrow

- Chemotherapy
- Allopurinol

Survival

1995

Lung Adenocarcinoma [16]

- Large mass
- Liver metastases

- Hydration
- Allopurinol
- Potassium and phosphate binders

Death

2000

Gastric Adenocarcinoma [17]

- Large mass > 7 cm in diameter
- Liver metastases
- Multiple lymph nodes

- Hydration
- Chemotherapy
- Allopurinol
- Alkalization
- Hemodialysis

Death

2001

Testicular germ cell tumor [18]

Case 1:
- Liver and lung metastases
- Bulky lymph nodes
Case 2:
- 20 × 25 cm retroperitoneal mass

- Surgery
- Chemotherapy
- Hemodialysis

Survival

2001

Colon cancer [11]

Liver metastases with necrosis

- Hydration
- Allopurinol
- Alkalization

Survival

2003

Hepatocellular carcinoma [11]

Large liver lesion

- Hydration
- Allopurinol
- Alkalization

Death

2003

Pheochromocytoma [11]

Large mass (20 cm diameter) with central necrosis

- Hydration
- Allopurinol
- Alkalization

Survival

2003

Prostate Cancer [19]

Liver and bone metastases

- Hydration
- Allopurinol
- Hemodialysis

Death

2007

Squamous cell Lung Cancer [12]

Advanced stage (stage IV)

- Hydration
- Hemodialysis
- Allopurinol
- Chemotherapy

Survival

2009

Maxillary sinus squamous cell carcinoma [20]

Liver metastases

- Hydration
- Rasburicase
- Allopurinol

Death

2009

Germ cell tumor [21]

- 14 cm Retroperitoneal mass
- Liver and lung metastases

- Hydration
- Rasburicase

Death

2010

Germ cell tumor [22]

20 × 17 × 13 cm pelvic mass

- Hydration
- Rasburicase
- Chemotherapy
- Surgery

Survival

2011

Small-cell lung cancer [10]

- Poorly differentiated tumor
- Liver metastases

None

Death

2011

Melanoma [23]

Extensive metastases (including liver and spleen)

- Hydration
- Hemodialysis

Death

2011

Hepatocellular carcinoma [24]

19.2 × 11 × 8 cm liver mass with extensive necrosis

- Hydration
- Allopurinol
- Hemodialysis

Death

2012

Small-cell lung Cancer [9]

- 4 cm obstructive lung mass
- Multiple liver metastases and extensive lymph nodes

Hydration

Death

2012

Adenocarcinoma of unknown primary [25]

- Liver metastases, possible lung and bone metastases
- Bulky retroperitoneal mass 14 × 13 cm

- Hydration
- Rasburicase
- Hemodialysis

Death

2012

Melanoma [26]

Liver metastases

Hydration

Death

2013

Renal cell carcinoma [13]

- 10 × 6.5 × 6.2 cm renal mass with necrosis
- Liver, bone, pleura, bronchus, adrenal glands metastases

- Hydration
- Allopurinol
- Hemodialysis

Death

2014

Cholangiocarcinoma [27]

Liver metastases

- Hydration
- Allopurinol

Death

2014

Hepatocellular carcinoma [28]

- 14 × 14 cm liver mass
-Multiple extensive lymph nodes

- Hydration
- Alkalization

Unknown (hospice/palliative care)

2014

Gastric Adenocarcinoma [29]

- Liver, bone and adrenal gland metastases
- Multiple lymph nodes

- Hydration
- Allopurinol
- Hemodialysis

Survival

2014

Skin Adenocarcinoma [30]

- Multiple subcutaneous, liver, kidney and adrenal gland metastasis

- Allopurinol
- Potassium binders
- Alkalinization

Death

2014

Pancreatic Adenocarcinoma [31]

- 6.7 × 10 cm mass
- diffuse liver metastasis and extensive lymph nodes

- Hydration
- Allopurinol
- Rasburicase

Death

2015

Small-cell lung cancer (our case)

- Liver, bone metastasis
- Extensive lymph nodes

- Hydration
- Rasburicase
- Allopurinol
- Alkalization
- Potassium binders
- Chemotherapy

Survival

2015

**Table 3.** Cairo-Bishop Laboratory Criterion
Variable	Value	Change from baseline
Diagnosis established by the presence ≥ 2 laboratory abnormalities 3 days before chemotherapy or 7 days after chemotherapy, if the patient has or will receive hydration and uric acid lowering agents.
Uric acid	≥ 8 mg/dL	25% increase
Phosphorus	≥ 6 mEq/L	25% increase
Potassium	≥ 4.5 mg/dL for adults and 2.1 mmol/L	25% increase
Calcium	≤ 7 mg/dL	25% decrease

Table 3. Cairo-Bishop Laboratory Criterion

Variable

Value

Change from baseline

Diagnosis established by the presence ≥ 2 laboratory abnormalities 3 days before chemotherapy or 7 days after chemotherapy, if the patient has or will receive hydration and uric acid lowering agents.

Uric acid

≥ 8 mg/dL

25% increase

Phosphorus

≥ 6 mEq/L

25% increase

Potassium

≥ 4.5 mg/dL for adults and 2.1 mmol/L

25% increase

Calcium

≤ 7 mg/dL

25% decrease

**Table 4.** Cairo-Bishop Clinical Criterion
Variable	Grade 0	Grade 1	Grade 2	Grade 3	Grade 4	Grade 5
Diagnosis established by the presence of at least one clinical finding not explained by treatment with chemotherapy or its side effects.
Creatinine	None	1.5 times ULN	> 1.5 - 3.0 times ULN	> 3.0 - 6.0 times ULN	> 6.0 times ULN	Death
Cardiac arrhythmia	None	No intervention	Non-urgent medical intervention indicated	Symptomatic and incompletely controlled medically or device-controlled	Life-threatening (arrhythmia with HF, shock, etc.)	Death
Seizure	None	None	One generalized seizure, seizures controlled by anticonvulsants or infrequent focal motor seizures not interfering with ADL	Seizures in which consciousness is altered; poorly controlled seizure disorder, with breakthrough generalized seizures despite medical intervention	Seizure which is prolonged, repetitive or difficult to control	Death

Table 4. Cairo-Bishop Clinical Criterion

Variable

Grade 0

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Diagnosis established by the presence of at least one clinical finding not explained by treatment with chemotherapy or its side effects.

Creatinine

None

1.5 times ULN

> 1.5 - 3.0 times ULN

> 3.0 - 6.0 times ULN

> 6.0 times ULN

Death

Cardiac arrhythmia

None

No intervention

Non-urgent medical intervention indicated

Symptomatic and incompletely controlled medically or device-controlled

Life-threatening (arrhythmia with HF, shock, etc.)

Death

Seizure

None

One generalized seizure, seizures controlled by anticonvulsants or infrequent focal motor seizures not interfering with ADL

Seizures in which consciousness is altered; poorly controlled seizure disorder, with breakthrough generalized seizures despite medical intervention

Seizure which is prolonged, repetitive or difficult to control

Death

**Table 5.** Risk Factors for the Development of TLS and STLS
Extensive tumor burden (bulky disease or disseminated disease)
Rapidly proliferating tumor
Extensive bone marrow involvement
Hepatic metastases
Highly chemosensitive malignancy
Elevated LDH level
Elevated uric acid level
Impaired renal function
Exposure to nephrotoxic drugs or uric acid excretion inhibiting drugs
Extrinsic compression of the urinary tract by the tumor
Dehydration, Infection or urinary obstruction

Table 5. Risk Factors for the Development of TLS and STLS

Extensive tumor burden (bulky disease or disseminated disease)

Rapidly proliferating tumor

Extensive bone marrow involvement

Hepatic metastases

Highly chemosensitive malignancy

Elevated LDH level

Elevated uric acid level

Impaired renal function

Exposure to nephrotoxic drugs or uric acid excretion inhibiting drugs

Extrinsic compression of the urinary tract by the tumor

Dehydration, Infection or urinary obstruction