Diagnosis

Diagnosis

Ixabepilone effect/injury, Helicobacter-associated gastritis.

Discussion

Ixabepilone is a chemotherapeutic agent, approved by the food and drug administration in 2007, for use in metastatic and locally advanced breast cancer. Ixabepilone is used when anthracycline and taxanes are no longer effective due to progressive disease, resistance, or when they are contraindicated due to toxicity. Ixabepilone is a semisynthetic analogue of the epothilone B class of drugs which stabilize microtubules resulting in mitotic arrest and apoptosis. Adverse events related to the gastrointestinal tract are not uncommon and may include nausea, vomiting, stomatitis, diarrhea, constipation, and abdominal pain. Ixabepilone has been reported to cause toxic erythema of chemotherapy and the histologic findings, in the skin, of epidermal keratinocytes in metaphase arrest (starburst cells) and apoptotic keratinocytes. However, there is essentially no literature on the histologic effects or findings of ixabepilone within the gastrointestinal tract mucosa.

The histologic changes within the gastrointestinal tract mucosa associated with ixabepilone, as exemplified in this case, are reminiscent of those of both taxanes and colchicine. Although these three medications belong to different drug classes and have different binding sites, they are all microtubule stabilizing agents, blocking mitosis and resulting in cell death. Therefore, they would all be expected to show similar histologic findings particularly mitotic arrest and ring mitoses. It is important to remember that identifying ring mitoses in a patient taking colchicine indicates toxicity while that is not true with taxanes. Taxanes also demonstrate florid apoptosis after the formation of ring mitoses, similar to the present case and the one described in the skin. Whether these histologic findings represent clinical gastrointestinal toxicity from ixabepilone is not entirely clear; however, the symptoms along with the endoscopic and histologic findings suggest the possibility of mucosal injury. This case emphasizes the importance of correlating the clinical history and findings, including the medication history, with the pathologic findings in any given case.

References

Cobham MV, Donovan D. Ixabepilone: a new treatment option for the management of taxane-resistant metastatic breast cancer. Cancer Manag Res. 2009;1:69-77.

De Petris G, Caldero SG, Chen, L, et al. Histopathological changes in the gastrointestinal tract due to drugs: an update for the surgical pathologist (part I of II). Int J Surg Pathol. 2014;22:120-128.

Millsop JW, Sharon VR, Petukhova T, et al. Chemotherapy reaction induced by ixabepilone, a microtubule stabilizing agent, mimicking extramammary Paget's disease in a patient with breast carcinoma. J Cutan Pathol. 2016;43:1215-19.

A portion of this case was presented at the College of American Pathologists Annual Meeting in 2019 in Orlando, Florida.

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