International Specimen Collection Recommendations and Submission Guidelines for Pathologic Evaluation of Unexplained Illness due to Possibly Infectious Etiology

Determining the cause of an infectious disease can be challenging, particularly when specimens such as serum, blood, or cerebrospinal fluid (CSF), a collection of the fluid around the brain and spinal cord, are unavailable, or when traditional laboratory assays have been unsuccessful at identifying a specific agent. Tissue-based diagnostics, utilizing specimens acquired through biopsy or autopsy provide extremely powerful and versatile methods of establishing an etiologic diagnosis. These samples, when submerged in 10% neutral buffered formalin (up to 14 days for biopsy or autopsy tissue, or up to 28 days for brain autopsy tissue), are almost always rendered non-infectious and can be transferred to 70% ethanol for long-term storage at room temperature until analysis by specific histopathologic, immunohistochemical or molecular assays.

For deceased patients, tissues obtained at autopsy are preferable; however, when an autopsy is impractical because of real or perceived biosafety risks, or because of cultural practices, limited tissue collection may still be possible and should be considered.

• When an autopsy is performed representative portions from all major organs (lung, heart, liver, kidney, spleen, and brain), as well as any tissues or organs that show conspicuous lesions or are indicated by clinical findings, should be submitted for evaluation.
• When a complete autopsy of a deceased patient is not possible a full-thickness biopsy should be collected from any conspicuous skin lesion (petechiae, eschar, or purpura). Core or wedge biopsy specimens of major organs (particularly liver), obtained by using a viscertome (a device used to get a liver tissue sample) or by limited autopsy, are also acceptable.

Biopsy specimens of skin, bone marrow, or other tissues, obtained from living patients, are also acceptable for evaluation.

All tissue specimens should be fixed in 10% neutral buffered formalin for a minimum of 3 days (72 hours) and up to 2 weeks (14 days) for biopsy or autopsy tissue, or up to 4 weeks (28 days) for brain autopsy tissue. Biopsy tissues should be paraffin-embedded prior to submission to IDPB. If not paraffin-embedded, after a minimum of 3 days (72 hours) of formalin-fixation, autopsy tissues can be transferred to 70% ethanol for long term storage and shipping at room temperature.

Each specimen MUST be labeled clearly with a unique patient identifier that includes the patient’s name. When available, a brief clinical history, including any pertinent laboratory results, should also be included.

Shipping Guidelines

• CDC does not accept routine shipments on weekends or holidays. Please make sure packages arrive Monday–Friday.
• For urgent cases, immediately contact IDPB for approval.
• Paraffin-embedded tissue blocks should be shipped refrigerated with frozen cold packs during hot summer months to prevent them from melting.
• Formalin-fixed wet tissue that is currently in formalin or has been transferred to 70% ethanol should be shipped in leak-proof containers at room temperature. The maximum volume of formalin per primary specimen container cannot exceed 30 mL (excess formalin should be discarded prior to shipping). The maximum net volume of formalin per shipping package cannot exceed 1 L. If the specimen is in 70% ethanol, discard most of the ethanol prior to shipping. Leakproof containers should be placed in double Ziploc style bags and sufficient absorbent padding material should be added to the outer bag to absorb any potential leaks. Ship for overnight delivery.
• All samples must be shipped in accordance with all applicable local, state and federal regulations. Upon shipment, submitter should send an email to IDPB (pathology@cdc.gov) providing shipping company, shipped date and package tracking number.
• An import permit is not required for non-infectious (formalin-fixed) specimens.
  • Specific regulations for Shipping and Packing are available from: CDC Specimen Management.

All specimens should be addressed to:

Dr. Jana Ritter
Centers for Disease Control and Prevention
1600 Clifton Rd NE
RDSB/STATT Unit 109
Atlanta, GA 30329-4027

Phone: 404-639-3132
Email: Pathology@cdc.gov