Diagnosis and Understanding the Pathology Report

Confirming a diagnosis of Congenital Tufting Enteropathy (CTE) is a process of gathering evidence from your baby’s clinical symptoms, the physical structure of their intestine, and their genetic code. Because the condition is so rare, the diagnosis often relies on specialized laboratory tests that look for very specific “hallmarks” of the disease ^[1][2].

The Role of Intestinal Biopsy

An intestinal biopsy is the most direct way to see how CTE is affecting your baby’s digestive tract. During this procedure, a doctor takes tiny samples of the intestinal lining to be examined under a microscope by a pathologist.

When you receive the pathology report, you may see several technical terms. Understanding these can help you feel more informed during meetings with your medical team:

• Villous Atrophy (or Blunting): Normally, the intestinal lining has finger-like projections called villi that absorb nutrients. In CTE, these villi are flattened or shortened (atrophied), which significantly reduces the body’s ability to absorb food. Note: Villous atrophy is not specific to CTE and is seen in many intestinal conditions. ^[3][1]
• Crypt Hyperplasia: The “crypts” are the glands at the base of the villi where new cells are born. In CTE, these crypts often become elongated or enlarged as the body tries unsuccessfully to replace the abnormal surface cells ^[1][2].
• Focal Epithelial Tufts: This is the “hallmark” of the disease. It refers to small, crowded clusters of cells on the surface of the intestinal lining that look like “tufts” or tear-drops ^[4][5]. Because these tufts can be sparse or “focal,” pathologists may need to look at multiple samples to find them ^[5][6]. If the exact word “tufts” is missing from an initial report, it does not completely exclude the diagnosis.

MOC31 (EpCAM) Staining

Pathologists use a specialized test called immunohistochemistry—essentially a chemical “stain”—to see if specific proteins are present in the tissue. For CTE, they often use a stain called MOC31, which looks for the EpCAM protein ^[7][8].

• In EPCAM-related CTE: The stain will often show an absence of the EpCAM protein, which supports an EPCAM-related diagnosis ^[8][3].
• In SPINT2-related CTE: The protein may be present but not working correctly, or it may be reduced. However, normal EpCAM staining does not rule out the disease, especially for SPINT2-related CTE. This staining is an adjunctive tool, not a definitive confirmation; molecular genetic testing is required ^[9][10].

Confirming with Genetic Testing

While the biopsy shows the damage, genetic testing identifies the cause. This is the most definitive way to confirm a diagnosis of CTE.

• Congenital Diarrhea Panels: Doctors usually start with a “multigene panel.” This is a single blood test that checks dozens of genes known to cause diarrhea in infants, including EPCAM and SPINT2 ^[11].
• Deletion/Duplication Analysis: Depending on the laboratory, testing may also include copy-number analysis to look for missing or duplicated pieces of DNA, though a negative panel does not perfectly exclude the disease ^[9][12].
• Next-Generation Sequencing (NGS): If initial tests are unclear, doctors may use advanced sequencing (like Whole Exome or Whole Genome Sequencing) to look at every gene in your baby’s DNA. This can be especially helpful if the presentation is atypical ^[13][3].

Empowering Your Advocacy

As a parent, you are an essential part of the diagnostic team. You have the right to request and keep copies of all pathology and genetic reports. Having these documents on hand is invaluable if you ever need to seek a second opinion or coordinate care between different specialists. When you look at the pathology report, look for the terms “tufts,” “villous atrophy,” and the results of the “MOC31” or “EpCAM” stain ^[7][8]. Seeing these terms confirmed in writing can help you feel more confident that your baby is receiving the correct care for their specific condition.