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Pituitary and sellar region pathology MML and sellar region pathology_MML.pdf MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION HARVARD MEDICAL SCHOOL Pituitary and sellar region pathology

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  • MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    HARVARD MEDICAL SCHOOL

    Pituitary and sellar region  pathology

    Maria Martinez‐Lage, MD Assistant Professor of Pathology, Harvard Medical School Assistant Pathologist, Massachusetts General Hospital

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    Anatomy

    Anterior pituitary or adenohypophysis

    Posterior pituitary or neurohypophysis

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    Pituitary Histology Anterior 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

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    Normal adenohypophysis Reticulin – normal pituitary architecture

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    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

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    Pituitary adenomas Most common lesion of the sella

    • Present in up to 25% of autopsies

    Detected clinically 10‐15% of all intracranial neoplasms Biochemically 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

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    Pituitary adenomas Genetics

    • 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 ‐

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    Pituitary adenoma Reticulin – normal pituitary architecture

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    Clinicopathologic classification

    Functioning adenomas Nonfunctioning adenomas

    G H ‐PR

    L‐TSH  fam

    ily

    GH‐producing

    ‐ Densely granulated somatotroph adenoma

    ‐ Sparsely granulated somatotroph adenoma

    ‐ 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

    A C TH  

    fam ily

    ACTH‐producing

    ‐ Corticotroph adenoma Silent corticotroph adenoma

    G onadotr

    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

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    Seminars in Diagnostic Pathology Volume 30, Issue 3, August 2013, Pages 158–164

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS 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

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS 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)

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    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

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS 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 plurihormonal adenoma

    • Acidophilic stem cell adenoma

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS 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 plurihormonal adenoma

    • Acidophilic stem cell adenoma Numerous fibrous bodies  with Cam5.2 staining

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS 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 plurihormonal adenoma

    • Acidophilic stem cell adenoma

    Crooke’s hyaline change: occurs in

    normal corticotrophs in the setting of

    increased corticosteroids

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS 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 plurihormonal adenoma

    • Acidophilic stem cell adenoma

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION Arch Pathol Lab Med—Vol 139, March 2015

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION Arch Pathol Lab Med—Vol 139, March 2015

  • HARVARD MEDICAL SCHOOL

    MASSACHUSETTS GENERAL PHYSICIANS ORGANIZATION

    The future?

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