Dr. S.L. Asa Pituitary and Parathyroid Pathology 1 Practical Procedures Practical Procedures for Problematic for Problematic Parathyroids and Pituitaries Parathyroids and Pituitaries Sylvia L. Asa, M.D., Ph.D. Pathologist-in-Chief and Medical Director, Laboratory Medicine Program University Health Network Senior Scientist, Ontario Cancer Institute Professor, Department of Laboratory Medicine and Pathobiology University of Toronto Pituitary Problems Pituitary Problems The autopsy pituitary: Grossing and handling The surgical specimen: Pituitary or not? If pituitary, hyperplasia or adenoma? If adenoma, what kind? What is this inflammation all about? S T T PL AL ACTH GH PRL PL AL The Autopsy Pituitary The Autopsy Pituitary
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Dr. S.L. Asa Pituitary and Parathyroid Pathology
1
Practical Procedures Practical Procedures for Problematic for Problematic
Parathyroids and Pituitaries Parathyroids and Pituitaries Sylvia L. Asa, M.D., Ph.D.
Pathologist-in-Chief and Medical Director, Laboratory Medicine ProgramUniversity Health Network
Senior Scientist, Ontario Cancer Institute
Professor, Department of Laboratory Medicine and Pathobiology University of Toronto
Pituitary ProblemsPituitary Problems
The autopsy pituitary: Grossing and handling
The surgical specimen: Pituitary or not?If pituitary, hyperplasia or adenoma?If adenoma, what kind?What is this inflammation all about?
S
T
TPL
ALACTH
GH
PRL
PL
AL
The Autopsy PituitaryThe Autopsy Pituitary
Dr. S.L. Asa Pituitary and Parathyroid Pathology
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Pitfalls in Autopsy PituitariesPitfalls in Autopsy Pituitaries
Infarcts and fibrosisBasophil invasion of the posterior lobeCrooke’s hyaline changeHypophysitisTumorsTumorsTumors
The Surgical Biopsy:The Surgical Biopsy:Is This PituitaryIs This Pituitary??
It Is Adenoma It Is Adenoma –– Is That EnoughIs That Enough??
NO!But what now?
Dr. S.L. Asa Pituitary and Parathyroid Pathology
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Prognostic Markers in Prognostic Markers in Pituitary TumorsPituitary Tumors
Best is still tumor typeBest is still tumor typeClinicopathologic features – size, invasionOthers suggested:» MIB-1 (<5%, 5-15%, >15%)» PTTG (same idea as MIB-1)» p27 (lost in corticotroph adenomas)» p53 (no proven value)
Xanthomatous HypophysitisXanthomatous HypophysitisThe least common form of primary hypophysitisResembles xanthomatous inflammatory processes elsewhere, such as xanthomatous cholecystitis, endometritis or pyelonephritisCystic on radiologic or surgical evaluationMay be a response to ruptured cyst???
The Role of the PathologistThe Role of the Pathologistin the Management of Patients in the Management of Patients with Pituitary Pathologywith Pituitary Pathology
To ensure correct diagnosisTo guide correct managementTo be responsible for ongoing investigations to determine pathogenesis and future therapies
ReferencesReferencesAsa SL: Tumors of the Pituitary Gland. Fascicle 22, Third Series, in The Atlas of Tumor Pathology, Armed Forces Institute of Pathology, Washington DC, 1998.(Fourth series in press)ASA SL: Practical Pituitary Pathology: What Does the Pathologist Need to Know? Arch Pathol Lab Med 2008;132:1231-1240 ASA SL, EZZAT S: The pathogenesis of pituitary adenomas. Nature Reviews Cancer 2002; 2:836-49.ASA SL, EZZAT S: The pathogenesis of pituitary tumors. Annu Rev Pathol 2009;4:97-126..
Dr. S.L. Asa Pituitary and Parathyroid Pathology
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Parathyroid ProblemsParathyroid Problems
Parathyroid or not?If parathyroid, hyperplasia or adenoma?What about carcinoma?
The The ““OldOld”” Approach to Approach to Parathyroid SurgeryParathyroid Surgery
Identify all parathyroid glandsRemove dominant pathologyBiopsy all other glands
→Put the onus on the Pathologist to make the diagnosis of hyperplasia vs adenoma» often wrong or impossible!
The The ““NewNew”” Approach to Approach to Parathyroid SurgeryParathyroid Surgery
Radioguided surgery identifies the dominant glandLimited approach traumatizes only that glandIntraoperative PTH measurement confirms resection of culprit lesion
→ Pathologist only needs to confirm that abnormal (cellular) parathyroid tissue was resected
Dr. S.L. Asa Pituitary and Parathyroid Pathology
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Parathyroid Parathyroid vsvs Thyroid on FNAThyroid on FNA
Parathyroid has delicate vascular patterns, small cell size and numerous, disperse, stripped nucleiParathyroid CAN have intranuclear inclusionsIHC can be applied to FNA samplesCyst fluid can be tested for PTH to distinguish a parathyroid cyst from a cystic thyroid lesion
Parathyroid Identification at Parathyroid Identification at Intraoperative ConsultationIntraoperative Consultation
PTH vs Thyroid vs Lymph node or ThymusSmaller follicles than thyroidClear cells usually PTH» Fat stains can help
» NB intracytoplasmic fat
Hassal corpuscles
Sometimes impossible
IHC: Thyroid vs Parathyroid TumorIHC: Thyroid vs Parathyroid Tumor
Chromogranin +Parathyroid hormone +
TTF-1 negative
Dr. S.L. Asa Pituitary and Parathyroid Pathology
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Hyperplasia Hyperplasia vsvs AdenomaAdenomaHyperplasia» multiple (>1) glands» poorly encapsulated» diffuse or nodular» comparable areas in
adjacent glands» all 3 cell types» mitoses but little
pleomorphism
Neoplasia» solitary» encapsulated» nodule » adjacent normal gland
no hypercellularity» chief cells predominate» nuclear pleomorphism
Criteria of MalignancyCriteria of Malignancyin Parathyroid Tumorsin Parathyroid Tumors
Large lesion (> 1g)Infiltrative (but so is hyperplasia!)Atypia, mitoses, calcification, necrosis and fibrous bands (none definitive)Vascular invasionMetastases
Worrisome Histologic Alterations Worrisome Histologic Alterations Following FNA of Parathyroid *Following FNA of Parathyroid *
InfiltrativeAtypia, mitoses, calcification, necrosis and fibrous bands Following FNA for cytologic diagnosis of mass, aspiration for PTH measurement, or ethanol ablation of known PTH tumor
* Based on WHAFFT, credit to Dr. V. A. LiVolsi
Atypia and Mitoses in Atypia and Mitoses in Parathyroid LesionsParathyroid Lesions
Carcinoma
Hyperplasia
Dr. S.L. Asa Pituitary and Parathyroid Pathology
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Necrosis and CalcificationNecrosis and Calcification
Ancillary Tests for Borderline CasesAncillary Tests for Borderline Cases
Parafibromin loss
ImmunostainsImmunostains
Negative Rb ↓
High MIB-1 ↑p53 positivity
ReferencesReferences
DeLellis RA: Tumors of the Parathyroid Gland. Fascicle 6, Third Series, in The Atlas of Tumor Pathology, Armed Forces Institute of Pathology, Washington DC, 1993 Apel RL and Asa SL: The parathyroid glands. In Endocrine Pathology, LiVolsi VA and Asa SL (eds), Philadelphia, Churchill Livingstone, 2002, pp. 103-147DeLellis RA, Lloyd RV, Heitz PU, and Eng C: Pathology and Genetics of Tumours of Endocrine Organs. Lyons, France IARC Press, 2004