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Practical lessons from salivary gland cases: Application of the Milan System
Güliz A. Barkan, MD, FIACProfessor of Pathology and Urology
Loyola University Medical Center, Maywood, Illinois, [email protected]
Twitter handle: @barkanga
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Loyola University Medical Campus
Loyola University Lakeshore campus
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DISCLOSURE
I have not had any significant financial interest or other relationship with the manufacturers of the products or providers of the services that will be discussed in my presentation.
•I am one of the associate editors of the Milan System for reporting salivary gland cytopathology•I am one of the authors of the Paris System for reporting urinary cytology•I am the Vice President elect of the ASC Executive Board•I am a member of the ABP Test Development Committee
FINANCIAL - NONE
NONFINANCIAL - SOME
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Case History
• 59-year-old woman s/p thyroidectomy (years ago at another institution) for Hashimoto’s thyroiditis, presents for re-evaluation of a multiple bilateral neck lymph nodes.
• The patient has no complaints aside from tenderness in an enlarged left upper cervical lymph node
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Left neck ultrasound
Morphologically suspicious left 2B lymph node with rounded contour measuring 1.1 x 1.0 x 1.8 cm
http://www.surgicalcore.org
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Immunohistochemistry
Pancytokeratin p63
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Immunohistochemistry on the cell block
POSITIVE
• AE1/AE3
• SMA (patchy)
• p63 (patchy)
NEGATIVE
• S100 • GATA3 • PAX 8 • TTF1• Thyroglobulin• Synaptophysin• CD 56
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What is the best diagnostic category for this case?
A. Neoplastic, Benign
B. Atypical
C. Neoplasm of uncertain malignant potential
D. Suspicious for Malignancy
E. Positive for Malignancy
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Differential Diagnosis - Clinical• Benign salivary gland with
lymphoepithelial sialadenitis• Benign lymph node within the
salivary gland or salivary gland inclusions in a lymph node?
• Metastatic thyroid carcinoma• Metastatic basaloid squamous
carcinoma
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Differential Diagnosis-Cytomorphology
• Benign salivary gland with lymphoepithelial sialadenitis• Benign lymph node within the salivary gland or salivary gland
inclusions in a lymph node?• Pleomorphic adenoma, cellular type• Basaloid neoplasms
– Basal cell adenoma/ carcinoma– Adenoid cystic carcinoma– Basaloid squamous carcinoma
• Neuroendocrine tumor• Metastatic thyroid carcinoma
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Differential Diagnoses?
Am J Clin Pathol 2002;117:103-108
Küttner Tumor Case
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Differential DiagnosesLymphoepithelial sialadenitis Case
Atlas of Salivary Gland Cytopathology: with Histopathologic Correlations . VandenBussche, Ali, Faquin, Maleki, Bishop
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Differential DiagnosesPleomorphic Adenoma Case
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Differential Diagnosis of Basaloid neoplasms in the salivary gland
Seethala R. Modern Pathology (2017) 30, S84–S95
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Differential DiagnosesBasal cell adenoma Case
Atlas of Salivary Gland Cytopathology: with Histopathologic Correlations . VandenBussche, Ali, Faquin, Maleki, Bishop
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Differential DiagnosesBasal cell adenocarcinoma Case
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Differential Diagnoses
Adenoid cystic carcinoma Case
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Differential DiagnosisAdenoid Cystic carcinoma Case
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Differential Diagnoses
Basaloid squamous ca Case
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Back to reality: How did we diagnose this case?
Lymph Node 2B, Left, Ultrasound Guided Fine Needle Aspiration:
Adequacy: Satisfactory for evaluation.
Interpretation: Cytological examination: SUSPICIOUS FOR BASALOID NEOPLASM. SEE COMMENT.
Comment: …The morphology and immunostaining pattern do not support an origin from thyroid; rather they raise the possibility of basaloid tumor arising from the salivary gland (tail of parotid). Excisional biopsy is recommended for definitive diagnosis.
Dr. Swati Mehrotra
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When need be, call a friend…
LYMPH NODE 2B, LEFT, ULTRASOUND GUIDED FINE NEEDLE ASPIRATION -SPECIMEN ADEQUACY: Satisfactory for evaluation. .. DIAGNOSIS: Ductal epithelial groups with basaloid features and mild atypia in a background of blood and lymphocytes.
. NOTE: ..There are basaloid groups of ductal salivary gland epithelium with mild atypia and admixed background lymphocytes. DDX: neoplasm, reactive changes of salivary gland in a background of chronic inflammation.
Dr. Bill Faquin
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Left Parotidectomy
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FINAL DIAGNOSIS
LEFT PAROTID TUMOR;PAROTIDECTOMY: -BASAL CELL ADENOMA, 1.8 CM, COMPLETELY EXCISED -TWO INTRAPAROTID REACTIVE LYMPH NODES -SEE COMMENT
COMMENT: The tumor is likely arising from benign salivary gland inclusions in an intraparotid lymph node.
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Is there a helpful IHC panel?
PanK LMWK HMWK p63 p40 S100 B-cat CD117 PLAG1
Tumor
PA + + + + + + - v +
BCA/
BCAdC
+ + + + + + + v v
AdCC + + + + + + - + (lum) -
P(LG)A + + + + - + - v v
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Molecular studies in salivary gland neoplasms
Tumor Type Chromosomal Translocation Gene Fusion
Pleomorphic Adenoma Rearrangement of 8q12:
t(3;8)(p21;112)
t(5;8)(p13;q12)
Rearrangement of 12q13-15:
t(3;12)(p14.2;q14-5)
ins(9;12)(p23;q12-15)
PLAG1
HMGA2
Adenoid Cystic Carcinoma t(6;9)(q22-23;p23-24)
rarely t(8;9)
MYB-NFIB
CAMSG/PLGA Family**
CAMSG, “classic” type
PLGA, “classic” type
t(1;14)(p36.11;q12)
t(x;14)(p11.4;q12)
PRKD1 E710D mutation
ARID1A-PRKD1
DDX3X-PRKD1
Not known
Adapted from Wenig BM. Atlas of head and neck pathology. 2016. Elsevier.
Michele Stoffel, MD, PhD.Univ of Wisconsin
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•Most cases with MYB-NFIB show diffuse MYB nuclear reactivity (C), which can be seen in fusion-negative cases as well. •This finding is specific to AdCC when strong and diffuse. •A breakapart FISH assay can be used to show MYB gene rearrangement (D).
Weinrab I. Adv Anat Pathol 2013;20:367–377)Pictures from Dr C. Moskaluk, University of Virginia
MYB
Adenoid Cystic Carcinoma
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• Nuclear b-catenin expression was examined in 22 basal cell adenomas; scores were– 2+ in 18 cases (81.8%),
– 1+ in three cases (13.6%),
– 0 in one case (4.5%).
• Expression was localized in the basaloid myoepithelial cells.
J Oral Pathol Med (2011) 40: 460–466
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Basal cell adenocarcinoma
Human Pathology (2015) 46, 255–259
Adenoid Cystic carcinoma
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The Milan System of Reporting of Salivary Gland Cytopathology
Drs. Diana Rossi and Bill Faquin
Diagnostic Category ROM* Management*
1. NON-DIAGNOSTIC 25% Clinical and radiologic
correlation/ repeat FNA
2. NON-NEOPLASTIC 10% Clinical follow-up and
radiologic correlation
3. ATYPIA OF UNDETERMINED
SIGNIFICANCE (AUS)
20% Repeat FNA or surgery
4. NEOPLASM
Conservative surgery or
clinical follow-up
Conservative surgery
i) Benign <5%
i) Uncertain Malignant Potential
(SUMP)§35%
5.SUSPICIOUS FOR MALIGNANCY 60% Surgery:
Correlate LG vs HG
6. MALIGNANT 90% Surgery:
Correlate LG vs HG
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What is the best diagnostic category for this case?
A. Neoplastic, Benign
B. Atypical
C. Salivary gland neoplasm of uncertain malignant potential
D. Suspicious for Malignancy
E. Positive for Malignancy
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Salivary Gland Neoplasm of Uncertain Malignant Potential:
•Diagnostic of a neoplasm; however, a diagnosis of a specific
entity cannot be made.
•A malignant neoplasm cannot be excluded.
Neoplasm
“Sump pump”
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Take home messages
• Reviewed morphological differential diagnosis of basaloid neoplasms in the salivary gland.
• Reviewed the available ancillary tests to differentiate. between the “basaloid neoplasms” in the salivary gland.
• Introduced the “SUMP” category of the Milan System of reporting salivary gland cytopathology
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Duomo di Milano 2015