Clinical History The patient is a 39-year-old female with a past medical history of hypertension, acromegaly and diabetes who was complaining of an increased frequency of headaches. Imaging studies including an MRI showed a 2.2 cm sellar mass with minimal enhancement. Imaging studies including an MRI showed a 2.2 cm sellar mass with minimal enhancement that was extending to the right cavernous sinus

An endoscopic endonasal approach (EEA) with surgical removal was performed. A small fragment of the mass was sent for intraoperative evaluation where a touch prep was performed and stained with H&E Please describe the histologic findings of the touch prep

Answer The touch prep was cellular showing sheets of discohesive monomorphic cells with “salt and pepper” nuclei and minimal atypia. In addition the majority of the cells showed characteristic pale, rounded paranuclear cytoplasmic inclusions. A diagnosis of pituitary adenoma – NOS was rendered.

Paranuclear inclusions

H&E Please describe the histologic findings on the H&E stain

Answer Histologically, the sections confirmed an adenoma showing monomorphic neuroendocrine cells growing in a sheet-like and trabecular fashion. The majority of the adenoma cells showed pale, acidophilic, spheroid paranuclear cytoplasmic inclusions similar to those appreciated during the intraoperative consultation. Some of these indented the nucleus, consistent with “fibrous bodies”

Question Which stain would be best to highlight these fibrous bodies?

Answer Cam 5.2

Question What is your final diagnosis?

Answer Growth-hormone producing pituitary adenoma

Discussion Growth hormone-producing adenomas (GH cell adenomas) comprise approximately 10% of all pituitary gland adenomas and are often associated with acromegaly and less often gigantism [1].

Discussion They can be divided into “pure” GH cell adenomas, which are composed almost exclusively of GH producing cells as well as “mixed” subtypes composed of GH producing cells and most commonly prolactin [2]. Mixed Somatotroph-Lactotroph Mammosomatotroph Acidic Stem Cell Adenomas “Pure” growth hormone producing adenomas have been ultrastructurally classified into two distinct subtypes: [3]. Densely granulated GH cell adenomas (DG-type adenomas) Sparsely-granulated GH cell adenomas (SG-type adenomas)

Discussion Fibrous bodies are pale, rounded, paranuclear cytoplasmic inclusions seen in growth-hormone producing adenomas of the pituitary gland. They are considered the histologic hallmark of the SG-type GH cell adenoma subtype [3]. They are composed of aggregated cytokeratin filaments and therefore cytokeratin immunostains will highlight the characteristic paranuclear spheres [4]. Ultrastructurally fibrous bodies are located in the Golgi region and are shown to be composed of type-2 microfilaments [5].

Fibrous body

Discussion The clinical importance of recognizing fibrous bodies in a pituitary adenoma is that SG-type adenomas typically show a much weaker immunoreactivity for growth hormone, thus their presence should raise the suspicion of a GH cell adenoma, even in the absence of obvious clinical manifestations [7].

GH immunohistochemistry

References Perry, A. and D.J. Brat, Practical surgical neuropathology a diagnostic approach, in Pattern recognition series2010, Churchill Livingstone/Elsevier: Philadelphia, PA. p. 1 online resource (388) p. 2. Kontogeorgos, G., Classification and pathology of pituitary tumors. Endocrine, 2005. 28(1): p. 27-35. 3. Obari, A., et al., Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form. Endocr Pathol, 2008. 19(2): p. 82-91. 4. Horvath, E. and K. Kovacs, Morphogenesis and significance of fibrous bodies in human pituitary adenomas. Virchows Arch B Cell Pathol, 1978. 27(1): p. 69-78. 5. Nishioka, H., J. Haraoka, and K. Akada, Fibrous bodies are associated with lower GH production and decreased expression of E-cadherin in GH-producing pituitary adenomas. Clin Endocrinol (Oxf), 2003. 59(6): p. 768-72. 6. Kiseljak-Vassiliades, K., et al., Clinical implications of growth hormone-secreting tumor subtypes. Endocrine, 2012. 42(1): p. 18-28. 7. Kovacs, K. and E. Horvath, Pathology of growth hormone-producing tumors of the human pituitary. Semin Diagn Pathol, 1986. 3(1): p. 18-33.