Originally classified as a variant of silent
corticotroph adenoma, silent subtype 3
adenomas are a distinct histologic variant of
pituitary adenoma of unknown cytogenesis. We reviewed the clinical, biochemical, radiological, immunohistochemical and ultrastructural features of 31 silent subtype 3
adenomas to clarify their cellular origin. Among 25 with clinical and/or radiological data, all were macroadenomas; there was cavernous sinus invasion in 30% of cases and involvement of the clivus in 17% of cases. Almost 90% of patients were symptomatic; 67% had mass effect symptoms, 37% were hypogonadal and 8% had secondary
adrenal insufficiency. Significant hormonal excess in 29% of cases included
hyperthyroidism in 17%,
acromegaly in 8% and
hyperprolactinemia above 150 μg/l in 4%. Two individuals with
hyperprolactinemia who were younger than 30 years had
multiple endocrine neoplasia type 1. Immunohistochemically, all 31
tumors were diffusely positive for the pituitary lineage-specific
transcription factor Pit-1. Although three only expressed Pit-1, others revealed variable positivity for one or more
hormones of Pit-1 cell lineage (
growth hormone,
prolactin,
thyroid-stimulating hormone), as well as alpha-subunit and
estrogen receptor. Most
tumors exhibited perinuclear reactivity for
keratins with the
CAM5.2 antibody; scattered fibrous bodies were noted in five (16%)
tumors. The mean MIB-1 labeling index was 4% (range, 1-9%). Fourteen cases examined by electron microscopy were composed of a monomorphous population of large polygonal or elongated cells with nuclear spheridia. Sixty-five percent of patients had residual disease after surgery; after a mean follow-up of 48.4 months (median 41.5; range=2-171)
disease progression was documented in 53% of those cases. These data identify silent subtype 3
adenomas as aggressive monomorphous plurihormonal
adenomas of Pit-1 lineage that may be associated with
hyperthyroidism,
acromegaly or
galactorrhea and
amenorrhea. Our findings argue against the use of the nomenclature 'silent' for these
tumors. To better reflect the characteristics of these
tumors, we propose that they be classified as 'poorly differentiated Pit-1 lineage
adenomas'.