2019/10/25 Conflict of Interest Disclosure • Member of the IQMH Cytopathology Scientific Committee A Pot-Pourri of Pitfalls in Non-GYN Cytopathology Cady Zeman-Pocrnich October 26, 2019 Objectives Outline • After this session on Non-GYN pitfalls, participants should be able to: Pitfalls I have encountered in the cytopathological diagnosis of: o Appropriately classify lesions from a variety of Non-GYN sites by correctly applying morphological • Neuroendocrine Lesions criteria, ancillary study criteria, and clues from the • Salivary Gland Tumours clinical history; • Thyroid Nodules o Reflect on diagnostic misses and near misses in Non-GYN cytopathology Outline Pitfalls I have encountered in the cytopathological diagnosis of: • Neuroendocrine Lesions • Salivary Gland Tumours • Thyroid Nodules 1
2019/10/25 Diagnosis? Pitfall? Pitfalls in the Cytopathological Dx of Pitfalls in the Cytopathological Dx of Neuroendocrine Lesions Neuroendocrine Lesions False Negative False Negative Missing Small Cell CA Missing Small Cell CA • Especially on BrBrush/BrWash/BAL • Relatively few malignant cells, single cells > clusters • Malignant cells misinterpreted as lymphocytes • Usually LBC Pitfalls in the Cytopathological Dx of Small Cell CA on CS vs LBC Neuroendocrine Lesions Small Cell CA on CS Small Cell CA on LBC Single cells & large tight Single cells & small False Negative clusters loose clusters Missing Small Cell CA Tight nuclear molding Loose nuclear molding Long strands of nuclear Nuclear elongation & • Especially on BrBrush/BrWash/BAL material few tangles • Relatively few malignant cells, single cells > clusters Scant cytoplasm Thin rims of cytoplasm • Malignant cells misinterpreted as lymphocytes • Usually LBC Necrosis = obvious Necrosis = subtle Single Cells & Large Tight Clusters Single Cells & Small Loose Clusters 2
2019/10/25 Small Cell CA on CS vs LBC Small Cell CA on CS vs LBC Tight Nuclear Molding Loose Nuclear Molding Long Strands of Nuclear Material Nuclear Elongation & Few Tangles Small Cell CA on CS vs LBC Small Cell CA on CS vs LBC Scant Cytoplasm Thin Rims of Cytoplasm Abundant Necrosis Droplets of Amorphous Material w/ Apoptotic Bodies Pitfalls in the Cytopathological Dx of How can this pitfall be Neuroendocrine Lesions avoided? • Pay attention to clusters • Before dismissing as a “lymphocyte,” consider size & shape • Be aware that the classical False Negative False Positive cytomorphological features of small cell CA as seen on CS are Overcalling Carcinoid Tumour Missing Small Cell CA not as well developed on LBC as Small Cell CA preps 3
2019/10/25 Pitfalls in the Cytopathological Dx of Pitfalls in the Cytopathological Dx of Neuroendocrine Lesions Neuroendocrine Lesions False Negative False Positive False Negative False Positive Overcalling Carcinoid Tumour Overcalling Carcinoid Tumour Missing Small Cell CA Missing Small Cell CA as Small Cell CA as Small Cell CA 4
2019/10/25 How can this pitfall be avoided? • Single cells & cells at edges of clusters appear bland and have ample cytoplasm • Absence of necrosis, apoptotic bodies, and mitotic figures • Clinical information • Cell block & Ki67 Cancer Cytopathology, Volume: 117, Issue: 1, Pages: 51-56 First published: 29 January 2009, DOI: (10.1002/cncy.20007) Pitfalls in the Cytopathological Dx of Neuroendocrine Lesions False Negative False Positive Misclassification • HGNECa ↔ PDAC • HGNECa ↔ PDSqCC • HGNECa ↔ Lymphoma • HGNECa ↔ Sarcoma CB Ki67 5
2019/10/25 Lymphoma Small Cell CA Ewing’s Sarcoma PD Adenoca, CRC origin Cancer Cytopathology, Volume: 117, Issue: 1, Pages: 51-56 Basaloid SqCC First published: 29 January 2009, DOI: (10.1002/cncy.20007) Outline How can this pitfall be avoided? • If you are going to call small cell CA based on cytomorphological Pitfalls I have encountered in the features alone, the cytomorphological features must cytopathological diagnosis of: be absolutely perfect • Immunostudies • Neuroendocrine Lesions • Second opinion for any case where the Ddx is small cell vs • Salivary Gland Tumours other • Thyroid Nodules • Clinical information 6
2019/10/25 Outline Pitfalls I have encountered in the cytopathological diagnosis of: • Neuroendocrine Lesions • Salivary Gland Tumours • Thyroid Nodules Diagnosis? Pitfall? 7
2019/10/25 Pitfalls in the Cytopathological Dx of Salivary Gland Tumours False Negative False Positive Misclassification • Calling something WT when it’s not Mucoepidermoid CA Pitfalls in the Cytopathological Dx of Salivary Gland Tumours False Negative False Positive Misclassification • Calling something WT when it’s not • Mucoepidermoid CA CC + Lymphocytes + “ oncocytes ” • Acinic cell CA “ Oncocytes ” in MucoEpCA Oncocytes in WT “ Oncocytes ” in Acinic Cell CA Pitfalls in the Cytopathological Dx of Salivary Gland Tumours Misclassification False Negative False Positive • Calling something WT when it’s not • Mucoepidermoid CA • Acinic cell CA • Calling something PA when it’s not • AdCyCa & other basaloid neoplasms 8
2019/10/25 Plasmacytoid • Naked nuclei • Not plasmacytoid Contour = Tight, rounded Contour = Irregular PA Our Case – not a PA! “fuzzy” PA Stroma Our Case = Desmoplasia! AdCyCa Stroma border Pitfalls in the Cytopathological Dx of Pitfalls in the Cytopathological Dx of Salivary Gland Tumours Salivary Gland Tumours Misclassification Misclassification False Negative False Positive False Negative False Positive • Not common (in our lab) due to use of diagnostic • BN ↔ LPN categories • BN ↔ Metastatic CA • Beware acceptable atypia in a PA – stay at LP • Beware of metaplasias (squamous, mucinous) • Beware of repair 9
2019/10/25 Outline Pitfalls I have encountered in the cytopathological diagnosis of: • Neuroendocrine Lesions • Salivary Gland Tumours • Thyroid Nodules Pitfalls in the Cytopathological Dx of Outline Thyroid Nodules Pitfalls I have encountered in the cytopathological diagnosis of: • Neuroendocrine Lesions Atypia Architecture Pitfalls Pitfalls • Salivary Gland Tumours • Thyroid Nodules Undercalling Overcalling Undercalling Overcalling Small Follicle Pattern Small Follicle Pattern Atypia Atypia Special Acknowledgement: Dr. M. Weir Pitfalls in the Cytopathological Dx of Pitfalls in the Cytopathological Dx of Thyroid Nodules Thyroid Nodules Architecture Atypia Architecture Atypia Pitfalls Pitfalls Pitfalls Pitfalls Undercalling Overcalling Undercalling Overcalling Undercalling Overcalling Undercalling Overcalling Small Follicle Pattern Small Follicle Pattern Atypia Atypia Small Follicle Pattern Small Follicle Pattern Atypia Atypia 10
2019/10/25 Before classifying as FN/HCN… Before classifying as FN/HCN… 1. Is there chronic thyroiditis? 1. Is there chronic thyroiditis? 2. Is there fragmentation? 2. Is there fragmentation? 3. Is evaluation of architecture limited due to blood clot? 3. Is evaluation of architecture limited due to blood clot? 4. Could this be parathyroid? 4. Could this be parathyroid? Chronic thyroiditis is easy to recognize when it looks like this… Chronic thyroiditis is harder to recognize when it looks like this… Or this… Or this… Lymphoid tangles & fibrosis “Sticky follicles” Lymphoid aggregates Not true microfollicles! 11
2019/10/25 Before classifying as FN/HCN… 1. Is there chronic thyroiditis? 2. Is there fragmentation? 3. Is evaluation of architecture limited due to blood clot? 4. Could this be parathyroid? All images: Dr. M. Weir What to do if fragmented groups are the predominant finding? • If very low cellularity insufficient • If cellularity meets adequacy criteria FLUS/HCL All images: Dr. M. Weir All images: Dr. M. Weir Before classifying as FN/HCN… 1. Is there chronic thyroiditis? 2. Is there fragmentation? 3. Is evaluation of architecture limited due to blood clot? 4. Could this be parathyroid? 12
2019/10/25 • Microfollicles Before classifying as FN/HCN… • +/- Colloid-like material • Tiny cuboidal cells, very uniform 1. Is there chronic thyroiditis? • Lateral/unusual location • Prior thyroidectomy 2. Is there fragmentation? • Hypercalcemia 3. Is evaluation of architecture limited due to blood clot? 4. Could this be parathyroid? Images: Dr. M. Weir Pitfalls in the Cytopathological Dx of Thyroid Nodules Atypia Architecture Pitfalls Pitfalls Undercalling Overcalling Undercalling Overcalling Small Follicle Pattern Small Follicle Pattern Atypia Atypia Parathyroid Hormone IHC Respect atypia , but… Respect atypia , but… Increase atypia threshold if… Increase atypia threshold if… 1. Chronic thyroiditis 1. Chronic thyroiditis 2. Cyst repair 2. Cyst repair 3. Hurthle cells 3. Hurthle cells 13
2019/10/25 Respect atypia , but… Increase atypia threshold if… 1. Chronic thyroiditis 2. Cyst repair 3. Hurthle cells Respect atypia , but… Increase atypia threshold if… 1. Chronic thyroiditis 2. Cyst repair 3. Hurthle cells Pap Society Bethesda Atlas Image: Dr. M. Weir 14
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