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.
• 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 type2 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
1. 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. 8291.
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.