Celiac disease 

 – Villous blunting with increased intraepithelial lymphocytes (see comment)

COMMENT: The duodenal biopsy shows *** villous blunting with increased intraepithelial lymphocytes. While these findings are consistent with celiac disease in the appropriate clinical context, they are somewhat nonspecific. The differential diagnosis also includes other food sensitivities, bacterial overgrowth, malnutrition, certain immunodeficiencies (e.g., CVID), and autoimmune enteropathy. Clinical and serologic correlation is recommended.


For cases with increased IELs and no or only mild villous blunting

– Increased intraepithelial lymphocytes with intact villous architecture (see comment)

COMMENT: These findings are nonspecific and have been described in association with a variety of conditions including mild celiac disease, other food sensitivities, certain infections (including Helicobacter gastritis), small intestinal bacterial overgrowth, certain medications (including NSAIDs), peptic injury, inflammatory bowel disease, immunodeficiencies, and systemic autoimmune disorders. However, in many cases, no specific cause is identified. Clinical correlation is recommended.



Peptic duodenitis 

– Peptic duodenitis (see comment)

COMMENT: The duodenal biopsy show fragments of duodenal mucosa with foveolar metaplasia and acute and chronic inflammation. Intraepithelial lymphocytes are not increased. The features are suggestive of peptic duodenitis. Clinical correlation is suggested.


– Focal active duodenitis (see comment)

COMMENT: The duodenal biopsy shows mild acute duodenitis. No features of celiac disease are seen. The differential diagnosis includes peptic duodenitis, medications (particularly NSAIDs), and, possibly, an infection. Clinical correlation is recommended.


Chronic duodenitis

Expansion of lamina propria with mild villous blunting, but without increased intraepithelial lymphocytes

  – Chronic duodenitis (see comment)

COMMENT: The duodenal biopsy demonstrate a mild expansion of the lamina propria by chronic inflammatory cells with some associated mild villous blunting. There is no significant increase in intraepithelial lymphocytes to suggest a gluten sensitive enteropathy. No granulomas are identified. The differential diagnosis includes a reactive duodenopathy (often ascribed to chronic acid exposure, such as can be seen with Helicobacter infection, or other chemical injury), infection, medication-effect, and inflammatory/immune-regulated disorders (including inflammatory bowel disease). Clinical and endoscopic correlation is recommended.


Eosinophilic enteritis 

  – Eosinophil-rich enteritis (with up to *** Eosinophils per single high power field) (see comment)

COMMENT: The *** biopsy show an eosinophilic enteritis with up to *** eosinophils per single high-power field. There is also eosinophil degranulation and microabscess formation. This finding is nonspecific and can be seen in association with a variety of other conditions including a food allergy, medication-effect, parasitic infection, Crohn’s disease, and systemic connective tissue diseases. The differential diagnosis also includes an eosinophilic gastroenteritis, which is a diagnosis of exclusion.  Clinical correlation is recommended.



Active Ileitis 

  – Acute Ileitis with ulceration (see comment)

COMMENT: The terminal ileum biopsy shows an acute ileitis with scattered neutrophils within the epithelium and lamina propria. There is also extensive exudate with granulation tissue consistent with ulceration. No definite architectural changes (such as villous blunting) are identified to confirm chronic/longstanding injury. No granulomas or viral cytopathic effect is identified. The primary differential diagnosis for these findings includes medication effect (particularly NSAIDs), certain infections, and an emerging inflammatory bowel disease. Clinical and endoscopic correlation is recommend.


Chronic Active Ileitis (concerned about Crohn’s Disease)

  – Chronic active ileitis with ulceration (see comment)

COMMENT: The terminal ileum biopsy shows an active ileitis with cryptitis and ulceration. There are also features of chronicity including apparent villous blunting and pyloric gland metaplasia. No viral cytopathic changes or granulomas are present. The random colon biopsies show no significant abnormality. While the observed findings could be compatible with the clinical impression of Crohn’s disease, other etiologies, including medication-effect (particularly NSAIDs) and an infection cannot be excluded histologically. Clinical and endoscopic correlation is recommended.


Pseudomelanosis duodeni

  – Pseudomelanosis duodeni

COMMENT:  The duodenal biopsies demonstrate collections of brownish pigment within the cytoplasm of lamina propria macrophages, mostly within the villous tips. The findings diagnostic of pseudomelanosis duodeni, which is a nonspecific, often incidental, finding associated with hypertension, gastric intestinal bleeding, renal failure, diabetes, and with particular medications, such as iron and antihypertensive medications.


Polyps & Tumors


Intestinal-type adenomas (can see in the ampullary and non-ampullary regions)

– Tubular adenoma

 – Villous adenoma


Ampullary-only adenomas

  – Non-invasive pancreatobiliary papillary neoplasm, with ***-grade dysplasia

  – Intra-ampullary papillary-tubular neoplasm


  – Well-differentiated neuroendocrine tumor (WHO grade ***) (see comment)

COMMENT: The small bowel biopsy show a proliferation of nests of cells with round nuclei and stippled chromatin. These cells show strong, diffuse staining with synaptophysin and chromogranin immunohistochemical stains, consistent with neuroendocrine differentiation. No necrosis or mitotic figures are identified. Overall, these findings are diagnostic of a well-differentiated neuroendocrine tumor.  A Ki67 stain shows a proliferation index of ***% (***/500 cells counted), consistent with a WHO grade of ***.

Note: If it is a biopsy, you may opt to report a “provisional” WHO grade (and defer final classification to the anticipated resection specimen).


Mesenchymal tumors

 – Inflammatory fibroid polyp

 – Gangliocytic paraganglioma


Non-neoplastic lesions

  – Heterotopic Pancreas

  – Gastric heterotopia

– Brunner gland hyperplasia/hamartoma


– Peutz-Jeghers polyp (see comment)

COMMENT: The small bowel polypectomy shows a hamartomatous polyp with a prominent, arborizing smooth muscle core and lobular architecture. These findings are classic for a Peutz-Jeghers polyp. Clinical and endoscopic correlation is recommended to determine if this patient has Peutz-Jeghers syndrome. It has been suggested that even patients with isolated Peutz-Jeghers polyps have an increased risk of malignancy (reference below).

Reference: Burkart AL et al. Do sporadic Peutz-Jeghers polyps exist? Experience of a large teaching hospital. Am J Surg Pathol. 2007 Aug;31(8):1209-14.


 – Inflammatory/Hamartomatous polyp (see comment)

COMMENT: The histologic sections show a polyp with edematous stroma, abundant inflammation, and dilated cystic glands.  These findings are diagnostic of an inflammatory and/or hamartomatous polyp. In isolation, this could represent a sporadic inflammatory reactive/hyperplastic process. However, in the setting of multiple polyps, this could suggest a polyposis syndrome (e.g., Peutz-Jeghers syndrome, Cronkhite-Canada syndrome, Cowden syndrome, etc…). Clinical and endoscopic correlation is recommended.


Last updated: 5/23/24