Additional Testing of Biopsy Tissues in Severe Mpox Infections

Patients who are severely immunocompromised are at risk for more severe and complex disease presentations. It can sometimes be difficult to determine which signs and symptoms may be due to mpox and which may be associated with other infections. In those cases, clinicians may choose to perform a biopsy of the affected tissue to help better understand the cause of specific symptoms and ensure appropriate patient management and care.

In cases where a biopsy is performed, CDC’s Infectious Diseases Pathology Branch (IDPB) is available to assist with testing of formalin-fixed, paraffin-embedded (FFPE) biopsy tissue specimens for orthopoxviruses and other infectious etiologies, as indicated.

Before submission of any specimens to CDC’s IDPB, FFPE biopsy specimens should undergo routine histopathologic evaluation at the clinical institution’s pathology laboratory. Routine immunohistochemical and special stains for other infectious etiologies (e.g., for fungal and bacterial organisms, herpes simplex viruses 1 and 2, cytomegalovirus, varicella zoster virus, adenoviruses) should also be performed when indicated by the clinical institution’s pathology laboratory.

IDPB’s evaluation can be helpful in patients with known mpox diagnoses and for whom biopsy procedures are conducted, if clinically indicated:

• With new or atypical lesions where it is unclear if the lesions are primarily due to mpox or another infectious cause, or secondary bacterial or fungal infections.
• With significant complications including but not limited to mucosal lesions, bowel lesions, severe lymphadenopathy, pulmonary nodular lesions, or severe conjunctivitis.

Submission of Biopsy Tissues

FFPE biopsy tissue can be submitted to IDPB for additional pathologic characterization and infectious disease testing including for orthopoxviruses.

U.S. health care professionals, please consult with your state health department before contacting CDC regarding submission of specimens.

Health departments or health care professionals should contact IDPB at pathology@cdc.gov regarding the case and to request pre-approval. DO NOT ship FFPE tissue specimens without prior approval from CDC’s IDPB.

Sample acceptance criteria:

• Formalin-fixed, paraffin embedded (FFPE) tissue blocks that have been submerged in formalin for ≤2 weeks prior to embedding in paraffin
  • Unstained slides may be acceptable for orthopoxvirus immunohistochemical (IHC) testing. However, evaluation for other infectious etiologies may be limited if only unstained slides are submitted. Slides must be cut <10 days prior to submission to CDC’s IDPB.
• Tissues demonstrate histopathologic findings consistent with an infectious process.
• Some biopsies may be small specimens. To maintain specimen integrity, we recommend existing FFPE tissue blocks be submitted as is, and not be split, which might further reduce available tissue in the block. FFPE tissue blocks that have been depleted due to removal of tissue sections from the block are not acceptable for testing and will be rejected.

If approved, please follow these instructions:

• FFPE tissue specimens SHOULD be sent at ambient temperature or on cold packs during summer months to prevent the paraffin from melting. FFPE tissue specimens SHOULD NOT be sent on dry ice as it can damage the specimens.
• For more information on how to send specimens, see: Pathologic Evaluation of Fixed Tissues for Possible Infectious Etiologies (CDC-10365).

For information regarding collection and submission of formalin-fixed autopsy tissue specimens, please see: Autopsy and Handling of Human Remains of Patients with Mpox