Case 4: Brain Tumors Eyas M Hattab, MD, MBA AJ Miller Professor and - - PowerPoint PPT Presentation

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Case 4: Brain Tumors Eyas M Hattab, MD, MBA AJ Miller Professor and - - PowerPoint PPT Presentation

Jan 09, 2023 14 likes •446 views

XXXII International Academcy of Pathology Congress King Hussein Bin Talal Convention Centre Amman, Jordan Day 3: Wednesday, October 17 th , 2018 18-SS-4: Contribution of Immunohistochemistry in Diagnostic Pathology Case 4: Brain Tumors Eyas M

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18-SS-4: Contribution of Immunohistochemistry in Diagnostic Pathology

Case 4: Brain Tumors

Eyas M Hattab, MD, MBA AJ Miller Professor and Chair Department of Pathology and Laboratory Medicine eyas.hattab@louisville.edu XXXII International Academcy of Pathology Congress King Hussein Bin Talal Convention Centre Amman, Jordan Day 3: Wednesday, October 17th, 2018

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Clinical History

51‐year‐old man with a history of recurrent strokes and a slowly growing suprasellar mass identified on imaging. The patient had the stigmata of Cushing syndrome and required treatment with RU‐486 prior to surgery. The patient underwent endoscopic nasal resection.

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Reticulin

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

IHC

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

IH IHC

  • + Synaptophysin
  • + Chromogranin
  • Anterior pituitary hormones
  • LMW‐CK/Cam5.2
  • MIB1
  • ?p53
  • ?Pituitary Transcription factors
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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

ACTH

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

CAM5.2

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

p53

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

MIB1

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

TPIT SF1 PIT1

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Diagnosis?

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Coricotroph adenoma, sparsely granulated

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Role of Transcription Factors in Classification of Pituitary Adenomas What about atypia, mitoses, high proliferation, p53?

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

2004 WHO Adenomas: IHC/EM‐based T erminology /Classification

ACTH‐secreting Densely granulated ACTH cell adenoma Sparsely granulated ACTH cell adenoma GH‐secreting Densely‐granulated GH cell adenoma Sparsely‐granulated GH cell adenoma GH/PRL‐secreting Acidophil stem cell adenoma Mammosomatotroph cell adenoma Mixed GH/PRL cell adenoma Gonadotropin‐secreting Gonadotroph cell adenoma PRL‐secreting Densely granulated PRL cell adenoma Sparsely granulated PRL cell adenoma TSH‐secreting TSH cell adenoma Silent Silent corticotroph adenoma subtypes 1 and 2 Silent adenoma subtype 3 Null cell Null cell adenoma Oncocytoma

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

2017 WHO Classification of Endocrine Tumors: Paradigm Shift

Adenoma classification/terminology largely based on adenohypophyseal cell lineage (± pituitary hormones)

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Pituitary Cytogenesis

Asa SL and Ezzat S. Annu Rev Pathol Mech Dis. 2009;4:97-126

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Cell Lineage Adenoma Classification

  • Follows main adenohypophyseal transcription

factors (PIT1, SF1, TPIT)

  • Refined by pituitary hormones and

ultrastructure characteristics

  • New terminology
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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

New Adenoma Terminology

  • Combines cell lineage AND hormone secretion

– Lactotroph adenoma (PRL‐secreting adenoma)

  • Derived from PIT1 lineage
  • Secretes prolactin

– Gonadotroph adenoma

  • Derived from SF1 lineage
  • +/‐ FSH/LH
  • “Null cell adenomas” staining for SF1 = gonadotroph

adenoma

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Adenoma Diagnostic Workup

  • Most achieved using pituitary hormone IHC
  • Can be refined by supporting IHCs (CAM5.2)
  • Transcription factors if necessary

– Null cell adenoma – PIT1‐positive pleurihormonal adenoma

  • EM rarely required

LMWCK (CAM5.2) Fibrous bodies SG somatotroph adenoma Acidophil stem cell adenoma Crooke hyaline change Corticotroph cell differentiation

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Adenoma Diagnostic Workup (IHC)

Adenoma

Anterior Pit hormones, +/‐ cam5.2 Positive Name accordingly Multiple hormones + PIT1 PIT1‐positive plurihormonal adenoma Negative Transcription Factors Positive Name accordingly Negative Null cell adenoma

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Adenoma Diagnostic Workup (IHC)

Adenoma

PRL, GH, ACTH, FSH, LH, TSH +PRL Lactotroph adenoma +ACTH Corticotroph adenoma +FSH or LH Gonadotroph adenoma +GH Somatotroph adenoma +TSH Thyrotroph adenoma + multiple hormones PIT1, SF1, TPIT Negative PIT1, SF1, TPIT

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

2017 WHO: Corticotroph Lineage(TPIT‐positive) Adenomas

Adenoma type Immunophenotype Transcription factor and

  • ther cofactors

Corticotroph adenomas Densely granulated adenoma Sparsely granulated adenoma Crooke cell adenoma Silent corticotroph adenomas ACTH, CK TPIT

Lloyd et al (eds). WHO Classifications of Tumours of Endocrine Organs. 2017

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

2017 WHO: “Grading” Changes

  • 2004 WHO:

– Adenoma (typical) – Atypical adenoma – Carcinoma

  • Diagnostic criteria for atypical adenoma:

– Poorly defined – Poorly reproducible – Not predictive of long term behavior

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

2004 WHO: Atypical Adenoma

  • Diagnostic criteria:

– Atypical features suggestive of aggressive behavior such as invasive growth – Elevated mitotic index – Ki‐67 labeling index ≥3% – Extensive nuclear p53 immunoreactivity

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Aggressive Adenomas

  • Clinically defined (deviates from the benign

clinical behavior of a typical adenoma)

  • Definition varies:

– A large, invasive, rapidly growing tumor – A tumor with early recurrence despite gross total resection – A tumor resistant to treatment (radiation and/or medical therapy)

  • “Aggressive” and “invasive” are often used

interchangeably

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

2017 WHO Recommendations:

  • “Atypical adenoma” terminology is ABANDONED.
  • No new classification by tumor grading
  • Clinically aggressive tumors, evaluate for

– Tumor proliferation (mitotic count and Ki‐67 index)‐no specific cutoff – Tumor invasion

  • No utility for p53 immunostaining on a regular basis
  • No specific recommendation on how to report
  • Does not require inclusion of invasion in pathologic reporting

– “emphasizes that adenoma invasion should be noted as an important prognostic feature in identifying clinically aggressive adenoma” – ?By MRI studies and/or intra‐operative impression

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

2017 WHO Recommendations:

  • Recognition of adenomas that have more

aggressive behavior regardless of their histological “grading”:

– “Special” subtypes – Elevated proliferative activity

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Likelihood of recurrence of pituitary neuroendocrine tumors

Low probability For recurrence High probability for Recurrence Malignant tumor Adenoma (typical) Adenoma with elevated Proliferative activity Pituitary carcinoma Special subtypes of Adenomas:

  • Sparsely granulated

Somatotroph adenoma

  • Acidophilic stem cell

Adenoma

  • Crooke cell adenoma
  • Silent corticotroph
  • PIT1‐positive

plurihormonal adenoma

Lopes MBS. Acta Neuropathol 2017;134:521‐535

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Coricotroph adenoma, sparsely granulated, with elevated proliferative activity (See Comment)

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U

Adenohypophyseal Cell Lineage Classification

Transcription factor Lineage Adenoma type PIT1 Acidophilic Lactotroph adenomas Sparsely granulated adenomas Densely granulated adenomas Acidophilic stem cell adenomas Somatotroph adenomas Densely granulated adenomas Sparsely granulated adenomas Mammosomatotroph adenoma Mixed somatolactotroph adenoma Thyrotroph adenomas PIT1‐positive plurihormonal adenoma SF1 Gonadotroph Gonadotroph adenomas TPIT Corticotroph Corticotroph adenomas Crooke cell adenomas Silent corticotroph adenomas Undetermined Null cell adenomas

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ACTH

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U SF1

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U SF1

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U PIT1

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U PIT1

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E M H AT TA B , M D , M B A L O U I S V I L L E . E D U PIT1