Cytopathological Analysis in the Diagnosis of Corticotroph Adenomas: Technical Note

Objective: To demonstrate the utility of cytopathological analysis in the diagnosis of adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas in Cushing’s disease (CD).

Background: CD is the result of hypercortisolism secondary to an ACTH-secreting pituitary adenoma. Surgical resection is the most effective therapeutic approach in CD, and positive histopathological confirmation of ACTH-secreting adenomas results in higher rates of remission signifying accurate localization and resection of the tumor. In many cases, however, histopathological confirmation of an ACTH-secreting adenoma on final pathology is absent. Small size, soft consistency, and tissue loss during surgery and/or postsurgical processing are some of the reasons a final pathological diagnosis of an ACTH-immunopositive adenoma may not be able to be established.

Methods: We reviewed the charts of two patients with a diagnosis of CD who underwent surgical resection of a pituitary microadenoma identified on MR imaging ([Fig. 1]). Clinical presentation, hormonal workup, imaging studies, operative notes, pathology reports, and postoperative biochemical follow-up were reviewed.

The tumor aspirate in both specimens was sent fresh in saline to pathology. The specimens were processed according to standard protocols used in a Clinical Laboratory Amendments (CLIA)-certified cytopreparatory laboratory. Cytospins and a cell block were prepared. A portion of one of the specimens was used to prepare two slides using the Cytospin method (Thermo Fisher Scientific, Waltham, Massachusetts, United States) and subjected to standard Papanicolaou staining. The remainder of the material was fixed in formalin, embedded in paraffin as a cell block and stained with hematoxylin and eosin. ACTH immunostain was also performed on the cell block of both specimens.

Results: Cytopathology was able to confirm an ACTH-secreting pituitary adenoma on permanent analysis in both patients ([Fig. 2]).

Discussion: Lack of histopathological confirmation of ACTH-secreting pituitary adenoma after surgical treatment for CD is frequent. The use of cytopathologic processing for analysis of small soft-tissue specimens in patients with CD undergoing surgery may help confirm a diagnosis of corticotroph adenoma. Processing of the tissue is critical to obtain positive results.

Fig. 1

Fig. 2