MARSH CLASSIFICATION - CELIAC DISEASE



The classic pathology changes of coeliac disease in the small bowel are categorised by the "Marsh classification".

As the clinical and endoscopic spectrum of CD has broadened, the range of histologic findings compatible with the diagnosis of serologically positive CD has also increased:

* Increased intraepithelial lymphocytes (IEL).This is the first and most sensitive marker of the effects of gluten on the small-bowel mucosa; thus, it is the major histological feature of CD. An increase is defined as >40 lymphocytes per 100 surface or upper-crypt enterocytes. The vast majority are CD2+, CD3+; 70 to 90% are CD8+ T-cells. In latent forms of CD, an increase in IELs is often the only abnormality; villous architecture and lamina propria cellularity are within the normal range. IEL counts should be performed on well-oriented villi in sections cut at 3- to 4- m thickness. Goldstein and Underhill have suggested that a clustering of lymphocytes ( 12) in the epithelium at the tips of villi and extending evenly down along the sides of the villus are a clue that CD may be present.

* Increased cellularity in the lamina propria. In CD with villous/crypt abnormalities, plasma cells, lymphocytes, and eosinophils are increased in number, particularly in the upper half of the mucosa. The number of eosinophils may be striking; however, their increase is paralleled by the increase in mononuclear inflammatory cells, a finding that is against a diagnosis of allergic enteritis. Neutrophils are also part of the inflammatory response and may be numerous in the lamina propria. However, if they are associated with cryptitis or crypt abscesses, an alternative diagnosis (such as autoimmune enteropathy, peptic injury, or Crohn's disease) should be considered.

* Enterocyte damage. In latent or minimal-deviation CD, the enterocytes are unremarkable. With severe injury, however, the apical cytoplasm is typically vacuolated; the cells themselves are shorter than normal and easily dislodged from the underlying basement membrane.

* Villous atrophy/crypt hyperplasia.These changes represent severe damage and can only be assessed in well-oriented sections. As a rule, villous-crypt ratios can be assessed if four or more crypts in parallel, nontangential array adjacent to one another can be identified in the biopsy specimen. Taking deeper sections through the tissue block may uncover such areas. Also, it should be recalled that villi overlying and adjacent to lymphoid nodules/follicles are normally blunted or absent, and such areas should not be chosen for analysis.

Pitfalls in the biopsy diagnosis of celiac disease

These include:
1. Inadequate number of biopsy pieces. The disease is patchy, this combined with the fact that all biopsy pieces may not be oriented sufficiently to assess the crypt to villous ratio means that at least 4 to 6 biopsy pieces need to be taken. Biopsy of the descending duodenum is sufficient.
2. Over-interpretation of villous atrophy because of poor orientation of the biopsies. If the pieces are not sufficiently oriented to assess the presence of, or degree of villous atrophy deeper cuts of the tissue block need to be ordered.
3. If the biopsy interpretation does not match either the clinical impression or serologic results the biopsy should be re-interpreted by a pathologist expert in the interpretation of gastrointestinal pathology.

NUCLEAR GRADE - RCC

FUHRMAN - GRADE I
tumor with small, round nuclei and inconspicuous nucleoli

FUHRMAN - GRADE II
tumor with round to slightly irregular nuclei with mildly enlarged nucleoli

FUHRMAN - GRADE III
tumor with round to irregular nuclei with prominent nucleoli


FUHRMAN - GRADE IV


tumor with enlarged pleomorphic cells




from http://www.medscape.com/viewarticle/446226_2