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Colon biopsies for evaluation of acute graft-versus-host disease (A-GVHD) in allogeneic bone marrow transplant patients.

Shidham VB, Chang CC, Shidham G, Ghazala F, Lindholm PF, Kampalath B, George V, Komorowski R - BMC Gastroenterol (2003)

Bottom Line: Some features, including intraepithelial lymphocytes in surface or crypt epithelium; and neutrophils, eosinophils, and edema in lamina propria, did not demonstrate significant difference in A-GVHD and negative controls.Pericryptal apoptosis, dilated crypts, irregular distribution of crypts, decreased lymphocytes, increased microvessel network, focal fibrosis, presence of muciphages, reactive changes in surface epithelium with mucin depletion, mucosal ulceration, and/or reduced mucosal thickness showed higher association with A-GVHD group.Its diagnostic significance was improved if intracyptal apoptosis was associated with features which were observed more frequently in A-GVHD group as mentioned above.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA. vshidham@mcw.edu

ABSTRACT

Background: Proper histomorphological interpretation of intestinal acute graft versus host disease (A-GVHD) associated with allogeneic bone marrow transplantation (BMT) is critical for clinical management. However, studies methodically evaluating different histomorphological features of A-GVHD are rare.

Methods: Colonic biopsies from 44 allogeneic BMT patients having biopsy-proven cutaneous A-GVHD were compared with colon biopsies from 48 negative controls.

Results: A-GVHD showed intra-cryptal apoptosis in 91% and pericryptal apoptosis in adjacent lamina propria in 70% (p < 0.002). Nonspecific apoptosis along the surface epithelium was observed in all groups with comparable frequency. The number of apoptotic cells in mucosa were approximately four times (5.3 per 10 HPF) the negative controls (p < 0.002) in A-GVHD group. 48% of cases with A-GVHD showed decreased number of lymphocytes in lamina propria. Some features, including intraepithelial lymphocytes in surface or crypt epithelium; and neutrophils, eosinophils, and edema in lamina propria, did not demonstrate significant difference in A-GVHD and negative controls. Pericryptal apoptosis, dilated crypts, irregular distribution of crypts, decreased lymphocytes, increased microvessel network, focal fibrosis, presence of muciphages, reactive changes in surface epithelium with mucin depletion, mucosal ulceration, and/or reduced mucosal thickness showed higher association with A-GVHD group.

Conclusions: Intracyptal apoptosis is a reliable indicator of A-GVHD. Its diagnostic significance was improved if intracyptal apoptosis was associated with features which were observed more frequently in A-GVHD group as mentioned above.

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Colonic biopsy with GVHD. A. Colonic mucosa with apoptotic bodies in crypts. Inset- Crypts show many apoptotic bodies (for higher magnification of the crypt with arrow see figure 1B). B. Magnified crypt shown in the inset of figure 1A: The crypt shows "popcorn" lesions (arrows) with occasional muciphages (arrowhead) in LP.
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Figure 1: Colonic biopsy with GVHD. A. Colonic mucosa with apoptotic bodies in crypts. Inset- Crypts show many apoptotic bodies (for higher magnification of the crypt with arrow see figure 1B). B. Magnified crypt shown in the inset of figure 1A: The crypt shows "popcorn" lesions (arrows) with occasional muciphages (arrowhead) in LP.

Mentions: The mucosal thicknesses (Table 2, A) from the surface epithelium to the internal limit of muscularis mucosa in three places were measured in the area of least thickness and mean was calculated. Thickness > 500 microns was considered within normal limits [20]. Cryptitis and crypt abscess were defined respectively as infiltration of crypt epithelium with neutrophils and presence of neutrophils in crypt lumen (Table 2, F). Five or fewer intraepithelial lymphocytes per 100 epithelial cells in surface and crypt lining were considered to be within normal limits (Table 2, G and H) [21]. We classified 1–5 extravascular neutrophils per 20 inflammatory cells in the lamina propria (LP) as mild increase and more than five as marked increase (Table 2, L). Macrophages with mucin as faintly basophilic foamy cytoplasm in H&E stained sections were identified as muciphages. Five or more muciphages in LP per 10 crypts were considered significant (Table 2, P). Presence of five or more endothelial lined blood spaces larger than 50 microns for every 10 crypts was regarded as increased microvessel network (Table 2, Q). Apoptosis (defined as single cell death) was indentified in H&E stained sections as apoptotic cells with scattered karyorrhectic basophilic globular intracytoplasmic debris of apoptotic bodies (Figure 1). Apoptotic cells were counted in 10 high power field (HPF) at 40 × magnification with a field diameter of 0.35 mm. Mitotic figures were counted per 10 crypts (Table 3).


Colon biopsies for evaluation of acute graft-versus-host disease (A-GVHD) in allogeneic bone marrow transplant patients.

Shidham VB, Chang CC, Shidham G, Ghazala F, Lindholm PF, Kampalath B, George V, Komorowski R - BMC Gastroenterol (2003)

Colonic biopsy with GVHD. A. Colonic mucosa with apoptotic bodies in crypts. Inset- Crypts show many apoptotic bodies (for higher magnification of the crypt with arrow see figure 1B). B. Magnified crypt shown in the inset of figure 1A: The crypt shows "popcorn" lesions (arrows) with occasional muciphages (arrowhead) in LP.
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Related In: Results  -  Collection

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Figure 1: Colonic biopsy with GVHD. A. Colonic mucosa with apoptotic bodies in crypts. Inset- Crypts show many apoptotic bodies (for higher magnification of the crypt with arrow see figure 1B). B. Magnified crypt shown in the inset of figure 1A: The crypt shows "popcorn" lesions (arrows) with occasional muciphages (arrowhead) in LP.
Mentions: The mucosal thicknesses (Table 2, A) from the surface epithelium to the internal limit of muscularis mucosa in three places were measured in the area of least thickness and mean was calculated. Thickness > 500 microns was considered within normal limits [20]. Cryptitis and crypt abscess were defined respectively as infiltration of crypt epithelium with neutrophils and presence of neutrophils in crypt lumen (Table 2, F). Five or fewer intraepithelial lymphocytes per 100 epithelial cells in surface and crypt lining were considered to be within normal limits (Table 2, G and H) [21]. We classified 1–5 extravascular neutrophils per 20 inflammatory cells in the lamina propria (LP) as mild increase and more than five as marked increase (Table 2, L). Macrophages with mucin as faintly basophilic foamy cytoplasm in H&E stained sections were identified as muciphages. Five or more muciphages in LP per 10 crypts were considered significant (Table 2, P). Presence of five or more endothelial lined blood spaces larger than 50 microns for every 10 crypts was regarded as increased microvessel network (Table 2, Q). Apoptosis (defined as single cell death) was indentified in H&E stained sections as apoptotic cells with scattered karyorrhectic basophilic globular intracytoplasmic debris of apoptotic bodies (Figure 1). Apoptotic cells were counted in 10 high power field (HPF) at 40 × magnification with a field diameter of 0.35 mm. Mitotic figures were counted per 10 crypts (Table 3).

Bottom Line: Some features, including intraepithelial lymphocytes in surface or crypt epithelium; and neutrophils, eosinophils, and edema in lamina propria, did not demonstrate significant difference in A-GVHD and negative controls.Pericryptal apoptosis, dilated crypts, irregular distribution of crypts, decreased lymphocytes, increased microvessel network, focal fibrosis, presence of muciphages, reactive changes in surface epithelium with mucin depletion, mucosal ulceration, and/or reduced mucosal thickness showed higher association with A-GVHD group.Its diagnostic significance was improved if intracyptal apoptosis was associated with features which were observed more frequently in A-GVHD group as mentioned above.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA. vshidham@mcw.edu

ABSTRACT

Background: Proper histomorphological interpretation of intestinal acute graft versus host disease (A-GVHD) associated with allogeneic bone marrow transplantation (BMT) is critical for clinical management. However, studies methodically evaluating different histomorphological features of A-GVHD are rare.

Methods: Colonic biopsies from 44 allogeneic BMT patients having biopsy-proven cutaneous A-GVHD were compared with colon biopsies from 48 negative controls.

Results: A-GVHD showed intra-cryptal apoptosis in 91% and pericryptal apoptosis in adjacent lamina propria in 70% (p < 0.002). Nonspecific apoptosis along the surface epithelium was observed in all groups with comparable frequency. The number of apoptotic cells in mucosa were approximately four times (5.3 per 10 HPF) the negative controls (p < 0.002) in A-GVHD group. 48% of cases with A-GVHD showed decreased number of lymphocytes in lamina propria. Some features, including intraepithelial lymphocytes in surface or crypt epithelium; and neutrophils, eosinophils, and edema in lamina propria, did not demonstrate significant difference in A-GVHD and negative controls. Pericryptal apoptosis, dilated crypts, irregular distribution of crypts, decreased lymphocytes, increased microvessel network, focal fibrosis, presence of muciphages, reactive changes in surface epithelium with mucin depletion, mucosal ulceration, and/or reduced mucosal thickness showed higher association with A-GVHD group.

Conclusions: Intracyptal apoptosis is a reliable indicator of A-GVHD. Its diagnostic significance was improved if intracyptal apoptosis was associated with features which were observed more frequently in A-GVHD group as mentioned above.

Show MeSH
Related in: MedlinePlus