SURGICAL PATHOLOGY OF ENDOCRINE AND ...

30 R.V. Lloyd et al.
Anterior Pituitary Cell Hyperplasia
Anterior pituitary cell hyperplasia is very uncommon [38,
39]. Causes of anterior pituitary hyperplasia may be primary
or idiopathic and secondary due to production of
hypothalamic releasing hormones from tumors such as pulmonary
or other neuroendocrine tumors producing GHRH,
CRH, or other hypothalamic hormones. Other causes of
secondary hyperplasia include end-organ failure such as
thyroid or adrenal cortical atrophy leading to stimulation
of TSH and ACTH cell proliferation, respectively, as part of
the negative feedback mechanism. Secondary hyperplasia
may also be related to hypothalamic hamartoma with production
of hypothalamic hormones [9, 35]. Hyperplasia
may be nodular or diffuse. Special stains such as reticulin
and immunohistochemical stains for collagen 4 and/or
pituitary hormones may help to establish the diagnosis of
hyperplasia. Reticulin and collagen 4 stains show expansion
of acinar unit. Immunohistochemical stains for specific
hormones may show enlarged clusters of cells of a specific
lineage in the expanded acini. The predominant cell type is
often admixed with other types of cells in the acinar unit. It
is important to appreciate the unique anatomical localization
of specific cell types in the anterior pituitary in order to
determine if the cells are increased. For example, ACTH
cells are located predominately in the mucoid wedge, so
the presence of abundant ACTH-positive cells in this
region may not indicate hyperplasia. In addition, basophil
invasion or the presence of abundant ACTH cells is
the intermediate zone equivalent in a normal physiological
change and does indicate ACTH cell hyperplasia.
PRL cell hyperplasia is present during pregnancy,
where the pituitary weight and number of PRL cells can
be increased up to two fold. Primary cell hyperplasia is
rare in human pituitaries. PRL cell hyperplasia has been
reported in the non-neoplastic pituitary cells adjacent to
PRL adenomas [38].
ACTH cell hyperplasia may be nodular or diffuse.
Nodular ACTH cell hyperplasia is characterized by an
increase in the acinar size, hyperthyroidal ACTH cells,
and expansion of the reticulin pattern. In contrast, diffuse
ACTH cell hyperplasia is characterized by an increase in
the number of ACTH cells, which may be more prominent
in the mucoid wedge without significant distortion of
the reticulin pattern. Patients with Addison’s disease and
adrenal cortical atrophy may develop diffuse and/or
nodular ACTH cell hyperplasia.
GH cell hyperplasia may be striking under certain
circumstances such as with GHRH producing tumors
in the lungs or pancreas. Histologically, there is an
expansion of the reticulin pattern with hypertrophic GH
producing cells. Bi-hormonal cells producing GH and
PRL may be present. Ultrastructural studies usually
show cells with large dense core secretory glands, welldeveloped
rough endoplasmic reticulin and prominent
Golgi-complexes.
Hyperplasia of TSH cells may be nodular and/or
diffuse. Patients with chronic hypothyroidism with
atrophy of the thyroid can develop TSH cell hyperplasia
with expanded acinar units and weakly staining TSHpositive
cells.
Hyperplasia of gonadotrophic cells is uncommon. It
may be associated with primary gonadal atrophy in a
patient with Klinefelter and/or Turner syndrome [9, 35].
Pituitary Adenomas
GH-Producing Adenomas
Most GH-producing adenomas are manifested clinically
as gigantism, if the tumor develops before the epiphyseal
plates have closed. This is usually characterized by
excessive linear growth. Acromegaly results when the
GH-producing tumor develops after puberty. Patients
usually develop increased stature, with enlarged extremities
manifested by increases in hat and (glove) sizes, prognathism,
and visceromegaly. The serum levels of IGF1 is
increased and may be more sensitive than increased serum
GH in establishing the diagnosis [9, 35].
Microscopic examination shows variable patterns
depending on the cellular composition. Acidophilic cells
are common (Fig. 2A), but chromophobic and amphophilic
cells may also be present. Immunohistochemical
staining is positive for GH, usually in a diffuse pattern
(Fig. 2B). Other cell types such as PRL and/or immunoreactive
alpha subunit cells may also be present in the
tumors. Various subtypes of GH adenomas have been
recognized, based largely on ultrastructural studies, which
usually correlate with immunohistochemical findings.
Densely Granulated GH Cell Adenomas
These tumors correspond to the classical type of GH
adenomas associated with acromegaly. These tumors are
characterized by slow growth and limited invasion into
tissues adjacent to the sella turcica. The tumors are
strongly positive for GH, but may also be reactive for
PRL, alpha subunit, and/or TSH. Ultrastructural
examination shows dense, core granules measuring
150–600 nm in diameter, with most secretory granules
between 400 and 500 nm in diameter (Fig. 2C) [7, 9, 35].