Page views in 2023: 334
Page views in 2024 to date: 68
14 June 2017 - Case of the Week #428

All cases are archived on our website. To view them sorted by case number, diagnosis or category, visit our main Case of the Week page. To subscribe or unsubscribe to Case of the Week or our other email lists, click here.

Thanks to Dr. Raul S. Gonzalez, M.D., University of Rochester Medical Center for contributing this case and Dr. Belinda Lategan, St. Boniface Hospital Winnipeg, Manitoba (Canada) for writing the discussion. To contribute a Case of the Week, first make sure that we are currently accepting cases, then follow the guidelines on our main Case of the Week page.




Advertisement


Website news:

(1) Please add NatPernick@gmail.com to your SafeList / Address book, so our email subscriptions go directly into your inbox.

(2) We have posted a revised Conferences page based on a new database, which makes it easier to add and remove conferences. The changes you will see include: conferences listed by organization (for organizations that post 6+ conferences at a time), total number of conferences on the page, and numbers of conferences per organization, location and subspecialty. There is also a cleaner look to the page. Let us know if you have any comments.

(3) Please bookmark / use our Amazon.com link in the Header, Footer, Books pages or many Book related banners, to shop at Amazon.com, and at the same time, help PathologyOutlines.com. We receive a commission (~ 5%) from all purchases made through this link, whether pathology related or not, at not cost to you. You get the benefit of wide selection of products and sellers, product reviews, a low price, and the knowledge that you are helping us maintain and expand our free website for the pathology community.

(4) Dr. Pernick has revised his 2011 paper, The Laws of Complexity and Self-Organization: A Framework for Understanding Neoplasia, click here. Please email him at NatPernick@gmail.com with any comments or questions.

Visit and follow our Blog to see recent updates to the website.



Case of the Week #428

Clinical history:
A 71 year old man underwent transanal endoscopic microsurgery for a large rectal tubuvillous adenoma. An incidental microscopic finding was noted in the specimen.


Microscopic images:

Various images



What is your diagnosis?


































Diagnosis:
Interstitial cell of Cajal hyperplasia (localized type)


Special stains:

CD117



Test question (answer at the end):

True or False:
The majority of interstitial cell of Cajal hyperplasia lesions are obligate precursors of gastrointestinal stromal tumors (GISTs) and demonstrate heterozygous somatic mutations of cKIT.

Discussion:

Interstitial cells of Cajal (ICC) function as "pacemakers" of the GI tract, initiating and maintaining peristalsis. They strongly express cKIT and DOG1 and variably express CD34. Hyperplasia of the interstitial cells of Cajal is the microscopic proliferation of these cells in the myenteric plexus of the gastrointestinal tract, regardless of the associated clinical milieu.

Microscopic images show focal proliferation of bland spindle cells with an irregular border located in the muscularis propria and extending into the pericolorectal soft tissue.

ICC hyperplasia may be focal or diffuse and occur in the setting of genetic syndromes or as a sporadic (incidental) finding. Sporadic or incidentally found foci of hyperplasia have an indolent course, and likely involute spontaneously. ICC hyperplasia seen in genetic syndromes (including germline mutations of cKIT, PDGFRA or NF1 or Carney’s triad with succinate dehydrogenase mutations) predispose to multiple gastrointestinal stromal tumors (GISTs) (Int J Clin Exp Pathol 2013;6:2989, Int J Surg Case Rep 2015;16:202). Most sporadic ICC hyperplasia lesions are seen in the distal esophagus, stomach or small intestine, with only rare lesions described in the colorectum (0.2% of routine specimens).

The nomenclature of incidental small proliferations of interstitial cells of Cajal is controversial. A four tier classification system has been suggested: ICC hyperplasia-localized type (≤5 mm, solitary), ICC hyperplasia-diffuse type (variable size, multiple or diffuse, may be confluent), GIST tumorlets (5-10 mm), and incidental, benign GISTs (>10-20 mm) (Int J Clin Exp Pathol 2010;3:549). Some authors prefer the term "microscopic GISTs", arguing the tendency of these lesions to infiltrate the surrounding muscularis propria suggests a neoplastic as opposed to hyperplastic nature. Others render a diagnosis of "benign GIST" only in asymptomatic, very small lesions (< 10 mm) incidentally found during abdominal surgery for other reasons, arguing that any GIST has the potential for metastasis. Tumor size and mitotic rate are the most important prognostic factors in GIST (Int J Surg Pathol 2002;10:81).

The differential diagnosis of these lesions from a morphologic perspective may include small foci of fibromatosis, inflammatory myofibroblastic tumor, leiomyoma and leiomyosarcoma. These four lesions do not typically express DOG1, and only rarely express cKIT (fibromatosis).

Localized hyperplasia of the interstitial cell of Cajal, as in this case, is usually a focal and incidental finding on microscopic examination, has an indolent course and demonstrates heterozygous somatic mutations in cKIT less commonly (~25%) than large or symptomatic GISTs (75 – 90%).

Additional references:

1. Rossi, S. et. al. Molecular and Clinicopathologic Characterization of Gastrointestinal Stromal Tumors (GISTs) of Small Size. (Am J Surg Pathol 2010;34:1480)

2. Streutker, C. J et. al. Interstitial cells of Cajal in health and disease. Part I: Normal ICC structure and function with associated motility disorders. (Histopathology 2007;50:176)

3. Streutker, C. J et. al. Interstitial cells of Cajal in health and disease. Part II: Normal ICC structure and function with associated motility disorders. (Histopathology 2007;50:190)

4. Agaimy A et. al. Microscopic gastrointestinal stromal tumors in esophageal and intestinal surgical resection specimens. A clinicopathologic, immunohistochemical, and molecular study of 19 lesions. (Am J Surg Pathol 2008;32:867)

5. Fletcher, CD, Berman, JJ, Corless, C, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. (Int J Surg Pathol 2002;10:81)


Test Question - Answer:

False.
Localized hyperplasia of the interstitial cell of Cajal, such as the case discussed here, is usually a focal finding incidentally noted on microscopic examination, has an indolent course and demonstrates heterozygous somatic mutations in cKIT less commonly (~25%) than large GISTs (75 – 90%).


Image 01 Image 02