December 14, 2009 (editorial adjustment 1/18/2011& thereafter)

To Whom It May Concern:

We are appealing the denial of the 88360 code⁸ for morphometric analysis, tumor immunohistochemistry (eg, HER-2, estrogen receptor & progesterone receptor, quantitative or semi-quantitative, each antibody, manual) for CD3 stains performed on duodenal or proximal small bowel biopsy specimens. The CD3 stains are performed to evaluate the specimen for evidence of all types of protein sensitive enteropathies (PSE), especially celiac disease. The CD3 immunohistochemical (IHC) stain highlights/amplifies intraepithelial lymphocytes (IELs). At low power, the pathologist "eyeballs" the biopsies for any suggestion of increased IELs and the representaiveness of adequate villi and even-ness of the IELs. Then the pathologist uses the amplification by the stain and manually counts (scores) the number of lymphocytes present per 20-cell cluster of villus-tip epithelial cells. Tips may have varykng scores, but the average score is reported. Once there is a VTS of 20 (one IEL per tip epithelial cell), it becomes impossible to count to a higher level. These results are then compared with accepted villous tip score standards (normal H&E VTS results are <5 and a 10 or higher CD3-amplified VTS is abnormal & 5-9 borderline) to determine if a diagnosis of PSE (& possible celiac disease) is warranted. So, a quantitative evaluation of the stain is required in order to accurately propose the diagnosis of celiac disease or some other PSE. Therefore, we respectfully request your reconsideration of this case.

CD3 marker studies on duodenal biopsies in patients with obscure signs and symptoms:

Due to the difficulty of cinching a diagnosis of the specific protein-sensitive enteropathy (PSE) of celiac disease (gluten-sensitive enteropathy…GSE) by serological testing and other means, we very successfully began some years ago to enhance the interpretation of the villous tip score (VTS) on these duodenal biopsies as a method of moving more decisively, histologically, toward that diagnosis.

It turns out, in the meantime, that there are many other protein-sensitive enteropathies (as with soy, tuna, chicken and other proteins).  The ONLY way to get a clue to any of those other causes of PSE (since there are no identifying serological tests) is by searching for increased intraepithelial lymphocytes (increased IELs).  Those other sign and symptom producing (gastric Helicobacter; medications such as NSAIDs) etiologies are known to produce elevated IELs ("IELosis"⁷); and detection with CD3 allows a possible explanation and dietary or situational adjustment to be made and avoid the simple wastebasket diagnostic disposition of “stress” or “functional problems”. 

Had our utilization of the CD3 IHC marker not been helpful, our gastroenterologists would not have been referred so many cases for work-up of these vague symptoms and signs.  By 2009, this has become state-of-the-art. 

References:

1. AJCP 116(1):63-71 (about VTS score and patterns), July 2001.
2. Biagi F, et. al., "Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease?", J. Clin Path 57(8):535-9 (about CD3 amplified visualization), Aug 2004.
3. Histopathology 54(7):783-795 (photos clearly showing advantage of counting with CD3), June 2009.
4. JAMA 302(11):1248 (for patients...how common CD is), Sept 2009.
5. JAMA 302(11):1171-1178 (increased death rate of those with CD), Sept 2009.
6. how VTS is routinely used in our lab...HERE.
7. Ensari A, "Gluten-Sensitive Enteropathy (Celiac Disease) Controversies in Diagnosis and Classification ", Arch. Path. & Lab. Med. 134:826-836, June 2010 HERE.
8. CAP CPT on-line: 88342 = qualitative IHC; 88360 = manual quantitative IHC; 88361 = computer-assisted (VIAS) quantitative IHC.
9. About celiac serologic & genetic testing...HERE and HERE.
10. The PSE decision tree or flow chart...HERE.
11. our 2002 letter to the editor Archives of Path...HERE.

(posted 2008; latest addition/adjustment 14 June 2011)