MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION
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Pituitary and sellar region pathology
Maria Martinez‐Lage, MDAssistant Professor of Pathology, Harvard Medical SchoolAssistant Pathologist, Massachusetts General Hospital
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Anatomy
Anterior pituitary or adenohypophysis
Posterior pituitary or neurohypophysis
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Pituitary HistologyAnterior pituitary or adenohypophysis• Derived from Rathke’s pouch
(evagination of the oropharynx)• Functional endocrine cells:
• “Acidophils” – GH, PRL• “Basophils” – ACTH, TSH, FSH,
LH
Posterior pituitary or neurohypophysis• Unmyelinated axons • Herring bodies correspond to
axonal accumulations of neurosecretory vesicles
• Cell bodies located in paraventricular and supraoptic nuclei of the hypothalamus
• Oxytocin and antidiuretic hormone secretion
• Pituicytes are cells of glial originPearse stain
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Normal adenohypophysisReticulin – normal pituitary architecture
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Sellar region pathology
Pituitary adenomas (85%)
Other relatively common lesions• Craniopharyngiomas (3%) • Rathke cleft cysts (2%) • Meningiomas (1%)• Metastases (0.5%)
Rare lesions• Hypophysitis• Pituicytoma• Spindle cell oncocytoma• Granular cell tumor of
neurohypophysis• Germ cell tumors (caveat in
pediatric population)• Histiocytosis
Arch Pathol Lab Med—Vol 139, March 2015
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Pituitary adenomasMost common lesion of the sella
• Present in up to 25% of autopsies
Detected clinically10‐15% of all intracranial neoplasmsBiochemically active (endocrine syndromes)
• Cushing’s disease (ACTH microadenoma)• Acromegaly/gigantism (GH)• Amenorrhea/galactorrhea (PRL)• Others are rare
Silent or nonfunctional (mass effect)• Headache• Bitemporal hemianopsia• Hypopituitarism
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Pituitary adenomasGenetics
• Up to 3% pituitary adenomas associated with genetic syndromes
• MEN1 (parathyroid, pancreas, pituitary) – most common• Mutations in MEN1 (menin) gene• Usually secreting prolactinomas
or somatotroph adenomas• Deletion of MEN1 has been
found in 10% of sporadic adenomas
Prevalence
• Lactotroph – 45‐50/100.000• Gonadotroph – 15‐20/100.000• Somatotroph – 10/100.000• Corticotroph – 5/100.000• Thyrotroph ‐ <1/100.000
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Pituitary adenomaReticulin – normal pituitary architecture
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Clinicopathologic classification
Functioning adenomas Nonfunctioning adenomas
GH‐PR
L‐TSH fam
ily
GH‐producing
‐ Densely granulated somatotrophadenoma
‐ Sparsely granulated somatotrophadenoma
‐ Mammosomatotroph adenoma
Silent somatotroph adenoma
PRL‐producing
‐ Lactotroph adenoma‐ Lactotroph with GH reactivity
(acidophil stem cell adenoma)Silent lactotroph adenoma
TSH‐producing
‐ Thyrotroph adenoma Silent tyrotroph adenoma
ACTH
family
ACTH‐producing
‐ Corticotroph adenoma Silent corticotroph adenoma
Gonadotr
opin fam
ily
FSH/LH‐producing
‐ Gonadotroph adenoma Silent gonadotroph adenoma
Unclassified
‐ Unusual plurihormonal adenoma Null‐cell adenoma
Asa, SL. Tumors of the Pituitary Gland AFIP Fascicle
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Seminars in Diagnostic PathologyVolume 30, Issue 3, August 2013, Pages 158–164
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MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION Courtesy of M. B. Lopes
Transcription factors are essential for the new WHO classification:
‐ Pit‐1: lactotrophs, somatotrophs, thyrotrophs‐ SF‐1: gonadotrophs‐ Tpit: corticotrophs
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MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION Courtesy of M. B. Lopes
The classification remains based on IHC for the main pituitary secreting hormones
Null cell adenoma is now defined by the lack of expression of both hormones and transcription factors (minimal alpha‐subunit expression allowed)
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How about “malignant potential”?WHO Classification (2004)
• Typical pituitary adenoma• Atypical pituitary adenoma (use abandoned in WHO2017)
Rare in incidence 5%‐15% 2. Not necessarily correlated with prognosis • Pituitary carcinoma (requires distant metastasis for diagnosis,
cerebrospinal and/or systemic )
Predictors of biological behavior• Ki‐67 proliferation index >3% (atypical)
WHO 2017: Ki‐67 should be evaluated but there is no specific cutoff value• P53 expression (unclear, no longer a factor)• Clinical evidence of aggressive behavior• Accurate immunohistochemical classification
Acta Neuropathol (2006) 111: 1–7
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Morphologic subclassification for prognostication: adenomas with potential for aggressive behavior
• Sparsely granulated somatotroph adenoma
• Crooke’s cell adenoma (corticotroph)
• Clinically silent corticotrophadenoma
• Pit‐1 positive plurihormonaladenoma
• Acidophilic stem cell adenoma
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Morphologic subclassification for prognostication: adenomas with potential for aggressive behavior
• Sparsely granulated somatotroph adenoma
• Crooke’s cell adenoma (corticotroph)
• Clinically silent corticotrophadenoma
• Pit‐1 positive plurihormonaladenoma
• Acidophilic stem cell adenoma Numerous fibrous bodies with Cam5.2 staining
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Morphologic subclassification for prognostication: adenomas with potential for aggressive behavior
• Sparsely granulated somatotroph adenoma
• Crooke’s cell adenoma (corticotroph)
• Clinically silent corticotrophadenoma
• Pit‐1 positive plurihormonaladenoma
• Acidophilic stem cell adenoma
Crooke’s hyaline change: occurs in
normal corticotrophsin the setting of
increased corticosteroids
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MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION
Morphologic subclassification for prognostication: adenomas with potential for aggressive behavior
• Sparsely granulated somatotroph adenoma
• Crooke’s cell adenoma (corticotroph)
• Clinically silent corticotroph adenoma
• Pit‐1 positive plurihormonaladenoma
• Acidophilic stem cell adenoma
HARVARDMEDICAL SCHOOL
MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION Arch Pathol Lab Med—Vol 139, March 2015
HARVARDMEDICAL SCHOOL
MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION Arch Pathol Lab Med—Vol 139, March 2015
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The future?