pituitary and sellar region pathology mml formattedpathology.massgeneral.org/hms/endo/pituitary and...

MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION

HARVARDMEDICAL SCHOOL

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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MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION

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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MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION

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

HARVARDMEDICAL SCHOOL

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

HARVARDMEDICAL SCHOOL

MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION

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

HARVARDMEDICAL SCHOOL

MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION

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

HARVARDMEDICAL SCHOOL

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

HARVARDMEDICAL SCHOOL

MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION

The future?