Definitions of Laboratory and Clinical Tumor Lysis Syndrome

The tumor lysis syndrome is the most common disease-related emergency encountered by physicians caring for children or adults with hematologic cancers. This syndrome occurs when tumor cells release their contents into the bloodstream, either spontaneously or in response to therapy, leading to the characteristic findings of hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. These electrolyte and metabolic disturbances can progress to clinical toxic effects, including renal insufficiency, cardiac arrhythmias, seizures, and death due to multiorgan failure.
In the current classification system of Cairo and Bishop, the tumor lysis syndrome can be classified as laboratory or clinical.
Definitions of Laboratory and Clinical Tumor Lysis Syndrome.*

Metabolic Abnormality	Criteria for Classification of Laboratory Tumor Lysis Syndrome	Criteria for Classification of Clinical Tumor Lysis Syndrome
Hyperuricemia	Uric acid >8.0 mg/dl (475.8 umol/liter) in adults or above the upper limit of the normal range for age in children
Hyperphosphatemia	Phosphorus >4.5 mg/dl (1.5 mmol/liter) in adults or >6.5 mg/dl (2.1 mmol/liter) in children
Hyperkalemia	Potassium >6.0 mmol/liter	Cardiac dysrhythmia or sudden death probably or definitely caused by hyperkalemia
Hypocalcemia	Corrected calcium <7.0 mg/dl (1.75 mmol/liter) or ionized calcium <1.12 (0.3 mmol/liter)†	Cardiac dysrhythmia, sudden death, seizure, neuromuscular irritability (tetany, paresthesias, muscle twitching, carpopedal spasm, Trousseau’s sign, Chvostek’s sign, laryngospasm, or bronchospasm), hypotension, or heart failure probably or definitely caused by hypocalcemia
Acute kidney injury‡	Not applicable	Increase in the serum creatinine level of 0.3 mg/dl (26.5 umol/liter) (or a single value >1.5 times the upper limit of the age-appropriate normal range if no baseline creatinine measurement is available) or the presence of oliguria, defined as an average urine output of <0.5 ml/kg/hr for 6 hr

* In laboratory tumor lysis syndrome, two or more metabolic abnormalities must be present during the same 24-hour period within 3 days before the start of therapy or up to 7 days afterward. Clinical tumor lysis syndrome requires the presence of laboratory tumor lysis syndrome plus an increased creatinine level, seizures, cardiac dysrhythmia, or death.
† The corrected calcium level in milligrams per deciliter = measured calcium level in milligrams per deciliter + 0.8 × (4 - albumin in grams per deciliter).
‡ Acute kidney injury is defined as an increase in the creatinine level of at least 0.3 mg per deciliter (26.5 umol per liter) or a period of oliguria lasting 6 hours or more. By definition, if acute kidney injury is present, the patient has clinical tumor lysis syndrome.

References:

1. Howard SC, Jones DP, Pui C-H. The Tumor Lysis Syndrome. N Engl J Med 2011; 364:1844-1854 [Medline]
2. Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol. 2008 Jun 1;26(16):2767-78. [Medline]

Revised Criteria for Hereditary Non-Polyposis Colorectal Cancer (Lynch Syndrome)

Amsterdam Criteria (1991)

Three or more relatives with colorectal cancer, plus all of the following:

• One affected patient should be a first-degree relative of the other two;
• Colorectal cancer should involve at least two generations;
• At least one case of colorectal cancer should have been diagnosed before the age of 50 years.

Amsterdam II Criteria (Revised International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Criteria 1998)

Three or more relatives with HNPCC-associated cancer (colorectal cancer or cancer of the endometrium, small bowel, ureter or renal pelvis) plus all of the following:

• One affected patient should be a first-degree relative of the other two;
• Two or more successive generations should be affected;
• Cancer in one or more affected relatives should be diagnosed before the age of 50 years;
• Familial adenomatous polyposis should be excluded in any cases of colorectal cancer;
• Tumours should be verified by pathological examination.

Modified Amsterdam Criteria

Just one of these criteria need to be met:

• Very small families, which can not be further expanded, can be considered to have HNPCC with only two colorectal cancers in first-degree relatives if at least two generations have the cancer and at least one case of colorectal cancer was diagnosed by the age of 55 years;
• In families with two first-degree relatives affected by colorectal cancer, the presence of a third relative with an unusual early-onset neoplasm or endometrial cancer is sufficient.

Revised Bethesda Criteria (2003)

Just one these criteria need to be met:

• Diagnosed with colorectal cancer before the age of 50 years;
• Synchronous or metachronous colorectal or other HNPCC-related tumours (which include stomach, bladder, ureter, renal pelvis, biliary tract, brain (glioblastoma), sebaceous gland adenomas, keratoacanthomas and carcinoma of the small bowel), regardless of age;
• Colorectal cancer with a high-microsatellite instability morphology that was diagnosed before the age of 60 years;
• Colorectal cancer with one or more first-degree relatives with colorectal cancer or other HNPCC-related tumours. One of the cancers must have been diagnosed before the age of 50 years (this includes adenoma, which must have been diagnosed before the age of 40 years);
• Colorectal cancer with two or more relatives with colorectal cancer or other HNPCC-related tumours, regardless of age.

References:

1. Chung DC, Rustgi AK. The hereditary nonpolyposis colorectal cancer syndrome: genetics and clinical implications. Ann Intern Med. 2003 Apr 1;138(7):560-70. [Medline]
2. Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005 May 5;352(18):1851-60. [Medline]
3. Pinol V, Castells A, Andreu M, Castellvi-Bel S, Alenda C, Llor X, Xicola RM, Rodriguez-Moranta F, Paya A, Jover R, Bessa X; Gastrointestinal Oncology Group of the Spanish Gastroenterological Association. Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA. 2005 Apr 27;293(16):1986-94. [Medline]