Pathology Grand Rounds, March 21, 2024: Esther Diana Rossi, MD, PhD

April 03, 2024

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Esther Diana Rossi, MD, PhD, MIAC, Division of Pathology and Histology, Catholic University, Agostino Gemelli School of Medicine, Rome, Italy, presents on, "The Milan System: Update from the 2nd Edition."

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00:00Good afternoon. Thank you for joining.
00:03We're going to get started right on time.
00:07I'm so excited to have Doctor
00:09Diana Esther Rossi here.
00:11It is my great pleasure to introduce
00:14her Doctor Esther Diana Rossi,
00:17whose fields of expertise
00:19and research are cytology,
00:20endocrine pathology and head
00:22and neck pathology. Dr.
00:23Rossi obtained her medical degree in
00:25anatomic pathology training at the
00:27University of Sacred Heart in Rome.
00:29Additionally, there she pursued APHD.
00:31In endocrine science and
00:33experimental metabolic endocrinology.
00:35Her thesis discussed molecular applications,
00:37specifically the B RAF mutation
00:39and papillary carcinoma and liquid
00:41based thyroid aspiration biopsies.
00:43During her residency training,
00:44Doctor Rossi was a visiting fellow at
00:46Upenn and Hahnemann in Philadelphia over
00:48the course of three consecutive years.
00:50Since that time,
00:52she has worked closely under the
00:54mentorship in an active collaboration
00:55with the late Doctor Virginia Volvosi,
00:57prior faculty member here in our
00:59department and well known as an icon
01:02in the field of endocrine pathology,
01:04specifically thyroid pathology.
01:05After residency training,
01:07Doctor Rossi stayed at Catholic University
01:09for her first academic appointment
01:11and continues to practice in the
01:13Division of Anatomic Pathology and Histology.
01:15As full Professor,
01:16Doctor Rossi is an active
01:18in International Society.
01:19She serves in many roles in Use
01:21Cap Companion Society since 2019.
01:23Some include the Use Cap Foundation
01:25Abstract Review Committee,
01:26Faculty for the Continuing Education Program.
01:30She's head of membership for the PAP Society,
01:32sits on the Executive Board,
01:34and just recently became president-elect
01:35of the PAP Society of Cytopathology,
01:38most notably as our first
01:40international candidates to serve
01:42in the Use Cap Companion Society.
01:44She's delivered short courses
01:46on salivary gland cytology since
01:482018 and will continue next week
01:50in Baltimore at the Use Cap.
01:52She's an invited speaker around
01:53the world for major international
01:55societies including the International
01:57Academy of Cytopathology Use CAP,
01:59the American Society of Cytopathology
02:01CAP and has Co directed courses at joint
02:04international meetings with the ASC.
02:06She's published over 150 manuscripts
02:08and high impact peer reviewed
02:11journals and the cytopathology,
02:13endocrine,
02:14head and neck surgical and molecular
02:16literature.
02:17Over half of those were first author
02:19and has published over a dozen book
02:21chapters more recently focusing on the
02:24classification systems of reporting
02:25thyroid and salivary gland cytology.
02:27Since 2017,
02:28she has served Associate editor for
02:30the Cancer Cytopathology and editor of
02:32the Atlas of Salivary Gland Cytology.
02:35She's lead author of the 5th edition
02:37of WHO for Pediatric Endocrine
02:38Head and Neck Heme and
02:40Lymphoid Blue Books. Doctor
02:43Rossi is a leading expert in the
02:45cytopathology classification and management
02:46of salivary gland lesions and neoplasms.
02:48She's Co editor with Doctor Fackin of
02:51the New Milan System for classification
02:53of salivary lesions and editor in
02:55chief of the 2nd edition of the
02:57Milan System published last year.
02:59She joins us today to share her
03:01experience in salivary gland lesions
03:02and the Milan classification System.
03:04It is truly our honor to host Doctor
03:06Rossi for Yale ground rounds today,
03:08an exemplary academic pathologist
03:10of our times.
03:11Thank you so much. Thank you,
03:13Thank you so much.
03:16Thank you so much for being here
03:19and to listen that to this talk
03:22about the Milan system and updates
03:25from the 2nd edition, no conflict of
03:28interest as you seen this morning.
03:30I'm really keen on movies,
03:31So when I think about the Milan system,
03:34but in general classification system
03:37comparing with the standard psychology,
03:40I think of this movie Mrs.
03:41Love Fire because she represented
03:44the other same side hub,
03:47Robin Williams.
03:48But why the development of an
03:51international system?
03:52If you think when we started there with
03:55this classification which was in 2015,
03:57there were classification for thyroid,
04:00for urine, for breast,
04:02but nothing for salivary and maybe
04:05this was you because the salivary
04:07is a little bit raver comparing
04:10with this other psychology and also
04:13because it's a little bit difficult.
04:15In fact, we have significant
04:18morphological overlapping,
04:19but we really were aware that we needed
04:22to put the different entities into
04:25categories linked with the risk of
04:29malignancy and specific strategies.
04:31And if you go back to the past,
04:33even at the end of the of the 18th century,
04:37La Wasier, a French chemist,
04:39underline that in order to improve the
04:41science, we need to improve the language.
04:44But also more recently,
04:45Leopold cast,
04:46one of the fathers of psychology,
04:49reported in his book that the
04:51reports should be expressed in a
04:54simple language that can be easily
04:57understood by the clinicians.
04:59Also in one of the 1st edition
05:01of The Who is the logical typing
05:03of salivary gland tumors?
05:04In 1972 in the general preface
05:08there was a note reporting that an
05:11internationally agreed classification
05:13of tumor acceptable and like all the
05:17different physicians would enable
05:19cancer workers are all around the world.
05:22When we started with this classification
05:24now there were some editorials
05:26such as this by Mandeep Mawa,
05:29a British surgeon emphasizing this.
05:32Is it time we adopted the
05:34classification for priority but in
05:36general for salivary gland setology?
05:39And the answer is yes,
05:40because when we started in 2015,
05:43there was a really a reporting confusion,
05:46confusion for salivary setology,
05:49diversity of diagnostic categories or
05:52discrete reports without categories or
05:56even surgical pathology terminology use on.
06:00We started with this classification
06:02and this idea during a meeting in a
06:05Bologna in two time February 2015.
06:07And then I shared this idea during
06:10the Youth Cup 2015 in Boston.
06:12We were in the lobby of the Hilton
06:15in the bar.
06:16So just think what might happen in a bar.
06:19And we decided all around we
06:21were with Doctor Falquin, Dr.
06:23Yale,
06:24Dr.
06:24Wychick that there was a general
06:27agreement on the need for a defined
06:30set of diagnostic categories for
06:32salivary cytology for different reasons,
06:35including a clarity of communication
06:37which means that the and improvement
06:40of cancer risk and also exchange
06:42of data across the different
06:44institution in a uniform way.
06:46This was the beginning of the Milan system.
06:48But why Milan?
06:49For thyroid we had Bethesda,
06:52For urine we have for urine we
06:54had Paris from the place in which
06:56they met for the first time
06:58for study very I really
07:00wanted an Italian name.
07:01But the occasion was also likely due
07:04to the fact that the first meeting of
07:07the core group of the Milan system was
07:10during the European Congress of Psychology,
07:13which likely, I have to say in
07:152000 and 15 September was in Milan,
07:18so very easy to name this classification
07:21after the place Milan and Italian name.
07:25The Milan system is so sponsored by the
07:27American Society and the International
07:29Academy of Setology for the 1st edition.
07:32The 2nd is also supported by the
07:34European Federation of Setology Society.
07:37I really need to to thank especially
07:39the American Society and the European
07:42Federation of Setology for the
07:43amazing job that they did with us.
07:45In our my intention, Dr.
07:47Faquin and I wanted a practical
07:50classification system that would be user
07:52friendly and internationally accepted.
07:55And also this is an evidence based system.
07:59We analyse all the cases from
08:02the 1980 to 2017 when we finished
08:05it with the prohibition some.
08:08Of course,
08:08there are several benefits when we think
08:10about the uniform reporting system,
08:12in this case staliberry.
08:13First of all,
08:14to improve communication between
08:17pathologists and clinicians,
08:18which means improve patient care,
08:21but also to facilitate scientological
08:25correlation.
08:25And to promote of course a research
08:28into the different fields among
08:30the different institutions try
08:32to speak a common language.
08:34Also for research and purposes,
08:38let's introduce the past life
08:40of the Milan system,
08:41the 1st edition and the new zone.
08:44I'll be interested.
08:45This is the international recently
08:47awarded movie with the 2nd edition.
08:50The past is represented by the 1st edition
08:53which was published in March 2018.
08:55As you can see here,
08:5710 chapters with definitions
08:59criteria as Planetary notes,
09:02over 40 contributing authors from
09:04all over the world 182 and 82 pages.
09:07109 Colour features several downloads
09:10and translations in different
09:12languages and on the right you can
09:15see the diagnostic categories 6 that
09:18we are going to describe soon with
09:21the risk of malignancy for each of
09:24them and the specific management for
09:28each of these diagnostic category.
09:31And really we want to global because
09:33we have gained it worldwide the
09:36acceptance amount the cytopathologist
09:37and you can see the Chinese and
09:40the Japanese Japanese version
09:42of the Milan system,
09:43but there is also a Turkish
09:46and the French translation.
09:49These are the major topics introduced
09:51by the Milan system first edition
09:53diagnostic category 6 combined
09:55with the risk of malignancy
09:57and the management strategies.
09:59The definition of a TPA of
10:01under term is significance.
10:03And the concept of a TPA in
10:05general also for salivary cytology
10:07as it was present in all the
10:09other classification systems.
10:11And emphasizing that the important
10:14role of ancillary techniques as
10:17an additional diagnostic tool
10:18school due also to the new upcoming
10:22genetic alterations since 2018
10:25/ 200 psychological publications
10:27are related to the Milan system
10:29from all over the world.
10:31Most have confirmed the risk of
10:33malignancy for each category,
10:35but mostly there has been a growing
10:38acceptance by the other network clinicians,
10:41which is the most important thing when
10:43you introduce a classification system.
10:45So in this golden age of the Milan system,
10:49why a second edition?
10:50Why should the postman reign twice?
10:53Because we realize from DSO 200 the
10:56publication that there was something
10:58that we needed to revise and to refine.
11:01The 2nd edition was published
11:03in July 2023 with new chapters,
11:07including a chapter specifically
11:09for ultrasound more and new
11:12hotters more pictures.
11:13We replace a half of them,
11:16the ambitions of the chapter with The Who
11:18had the knack because of Doctor Faquin and I.
11:21But also other holders were involved
11:24in this WHO 2022 changes in the risk
11:28of malignancy for each of the chapter
11:31and updates in the ancillary chapter.
11:33So we can say that we started from scratches.
11:36So these are some drawing done by
11:40Michelangelo in the secret room under
11:42the old Chapel in San Lorenzo, Florence.
11:45And you can see fingers, arms,
11:48hands that prepared himself to the
11:51final masterpiece which is the
11:54amazing assistant Chapel.
11:56And the same here's a for Rehauser.
11:58Because if you think about what's
12:00new in this last weekend months,
12:03of course I start with my passion movies.
12:06So Oppenheimer in the same period
12:08something like Barbie,
12:10something more social rusty,
12:11something more historical.
12:13Napoleon and also the 2nd edition
12:16of the Milan system, July 2023.
12:20The same orders and editors.
12:22Dr.
12:23Faquin and I, the same associate
12:26editors from Europe and from US.
12:28Yeah, you can compare the two
12:31different editions 2018,
12:33two 1023 in the second edition,
12:3511 chapters.
12:37The same definitions,
12:39criteria,
12:39explanatory notes is pretty similar
12:41to the of course the 1st edition,
12:44but both of them are similar to
12:47the Bethesda thyroid.
12:48We were involved of course,
12:50also in the Bethesda,
12:51so we wanted that there was a uniform
12:54evaluation by the readers of all these
12:56different heartless more than 60 now
12:59contributing others more than 250 pages,
13:03more than 200 colour pictures.
13:06We replace half of them exhibitions
13:08according of course to The Who,
13:10especially with the
13:12differences in the entities,
13:14changes in the risk of malignancy,
13:16and updates in the ancillary chapter.
13:19This is the general scheme,
13:20including UC 11 Chapter.
13:22Chapter 9 is the Imaging of Salisbury Grants,
13:26which was written by radiologists,
13:28specifically radiologists
13:30from Upenn from Pennsylvania.
13:33And this is the new core of the Milan system.
13:35So the diagnostic categories
13:37combined with the new risk of
13:40malignancy and the management,
13:42you can see also the sensitivity,
13:44specificity,
13:45positive and negative predictive
13:47value and the diagnostic
13:49accuracy which were pretty high.
13:51The first chapter here is overview
13:53is an overview of the evaluation of
13:56salivary cytology as it is present in
13:59all the different classification systems.
14:01From chapter two we started with
14:03the day of course the definition
14:05of the different categories and of
14:08course the 1st is non diagnostic
14:10risk of malignancy.
14:11Now is a
14:1215%. In the 1st edition
14:14was between 0 and 20%.
14:16We had an introduction and then a
14:19detailed discussion of all the criteria
14:21that you can here on the left on
14:23the right rear of absence of cells,
14:25poorly prepared samples we artifact.
14:28So for instance when you have a drying
14:31poor fixation crash artifact which
14:34hamper which for which you are a hamper
14:37it to make a diagnosis or the evidence
14:41of non neoplastic normal acinar cells.
14:44So basically you didn't sample
14:46the lesion and of course in the
14:49inhabitants of a clinically and
14:50radiologically they define mass.
14:52So you didn't sample yet the
14:54presence of a fibrosis stromal
14:57component alone with our cells,
14:59but also non mucinosis.
15:00The fluid with our cells saw only
15:03macrophages for instance and necrotic debris,
15:06but we will discuss about necrotic debris.
15:08As for the betesa thyroid,
15:10we included also some exceptions,
15:12for instance any salivary has parade in
15:14which you have even a few focal typical
15:17cells cannot be defined as non diagnostic.
15:20This should be defined as AUS,
15:23as atypia or mucinosis the
15:25fluid only without cells.
15:28This cannot be defined as non diagnostic
15:31but AUS because could be a mucosal
15:33or a retention cyst but also a low
15:36grade Mac and you sample only the
15:39mucinos component or the presence
15:41of abundant inflammatory cells.
15:43Without an epitelial component cannot
15:45be defined as non diagnostic because
15:48this should be interpreted and has
15:50had weight and also the evidence of
15:53stroma component which is associated
15:56with your plastic condition.
15:57Again even with our cells cannot
15:59be defined as non diagnostic.
16:01Just an example this is a cellulose mirror.
16:04About that you know a lot of
16:06the crush artifact,
16:07a lot of blood hampering
16:10diagnosis or here on the left you
16:12can see the absence of cells,
16:15so this is non diagnostic.
16:17Or in the left bottom you can see just
16:20a cluster of normal as inner cells.
16:23So this means that you didn't
16:25sample deletion.
16:26In the upper right you can see necrotic
16:29component associated with inflammatory cells.
16:31You have to diagnose this as non diagnostic.
16:34But it's important to put a
16:37note emphasizing that necrotic
16:38component is associated also with
16:41the neoplastic condition.
16:43So a sort of hub warrant about the
16:46habitats of necrotic component.
16:48And on the bottom you have this dance
16:51mucinos component which cannot be
16:53defined as non diagnostic because
16:55it can be neck or can be a benign
16:58condition a mucosal or retention system.
17:00Let's go to the the go to the
17:02bed and the ugly plaintiffs water
17:04hand cell drop by cell.
17:06Juliana did not neoplastic the
17:09risk of malignancy is now 11%
17:12in the 1st edition was 10%.
17:14We included all the non neoplastic condition,
17:17so metaplastic inflammatory
17:20acute chronic Cellulitis,
17:22lymphopitelial cell adenitis and
17:24the hyperplastic reactive lymph
17:26node especially in the parotid.
17:29You can see here some example,
17:30on the left we have a chronic
17:33cell Adenitis with the DS,
17:34small atrophic ductal cells and
17:37inflammatory component or on the
17:40on the right upper part Cellulitis,
17:43Cellulitis with the meta plastic
17:46ductal cells and chronic inflammation.
17:49Or in the bottom you can see some stones.
17:52And also this is an example of an acute
17:55cell Adenitis in which you have this
17:59clear acute inflammatory component in
18:01which it's important to come combine
18:04with the radiological and clinical
18:06evidence or for instance crystalloids
18:08which are frequently associated with
18:10inflammatory component and you can
18:12see the different shapes of that.
18:15Another possibility is a lymphobidila
18:17celladenitis in which usually you
18:20have a datum with a plastic squamid
18:23cells intermingled with a small
18:25lymphocyte and it's a typical habitance
18:28on cytology and not very difficult.
18:32But another possibility here is the
18:34reactive but lymph nodiperplasia in which
18:37you have the habitants have lymphocytes,
18:39a small lymphocytes,
18:41follicular dendritic cells,
18:43but also the habitants in C&amp;D
18:46tingible body macrophages.
18:47So just to remember that of course
18:50we might have this possibility
18:52also has non neoplastic.
18:54When you have some doubts that
18:56you can perform for instance a
18:58flow cytometry to solve the issue,
19:00we discussed it a lot about
19:02actipia and neoplasms,
19:03if they are different or not,
19:04like Jack Nicholson and the final Joker.
19:07And yeah,
19:08based on the literature we decided
19:10to stay with the same classification
19:13that we had in the first edition.
19:15So AUS and neoplasm super
19:18classified as B9 and sample.
19:21This is a table from the 2nd edition in which
19:24you can see the sober classification of AUS.
19:26The first he is a cystic and non cystic.
19:30For the cystic it's important to
19:31recognize if it is a mucinous component,
19:34so can be non neoplastic or
19:36can be neoplastic and the most
19:38important the plastic is Mac.
19:40If it is non Mucinosa you might have
19:43lymphocyte prevalent for instance and
19:45we have to consider the neoplastic or
19:47non neoplastic Consider and conditions
19:50but also epithelial cell prevalent and
19:53you have to recognize the different
19:55type if one possible squamoid,
19:57oncocytic, basaloid,
19:58acinic and spindle cells.
20:02And for each of them you might
20:04have non neoplastic and neoplastic
20:06conditions which are all described
20:08with bacteria with examples.
20:10And details in the in the system,
20:13in the in the Atlas.
20:14For non cystic,
20:15again we might have a typical lymphoid
20:18proliferation but also epithelial
20:20cell predominant with the same sober
20:24classification that we reported in non
20:27musinos epithelial cell prevalent.
20:29The risk of malignancy for this
20:31category is at around now 30%.
20:33In the 1st edition was 20%.
20:35Of course we are discussing
20:37about a surgical follow up.
20:40I would like to remember that for AUS
20:43the the best standard management is a
20:45follow up or repetition mostly repetition.
20:48So the data in this 30% is based on those
20:53cases that add a surgical follow up,
20:56we introduced it also the concept
20:58of risk of neoplasm in the first
21:01additional was not and 63% you can see
21:04is lower than sample which was 90%.
21:07We added the new tables describing
21:09all the different possible
21:10morphological scenarios as you can see here.
21:13Why? Because from the literature
21:15we realized that there's different
21:18scenarios have different risk of neoplasm
21:20and different risk of malignancy.
21:22And specifically the highest
21:24were for lymphocytes,
21:25Rich and the mucinos and the new table
21:28of course and additional sample records,
21:31just a few examples.
21:32On the left you can see
21:34a few a typical cells.
21:35This cannot be defined as non diagnostic.
21:38This should be considered as AUS
21:40or in the bottom a single cluster.
21:42Not enough for any conclusion
21:45because of the most important word
21:48associated with AUS is limitation
21:50in quality and quantity.
21:52So we are not sure that this is a
21:55reactive or any plastic condition
21:57and for this reason we need
21:59a repetition of the of the,
22:01of the of the category.
22:02Of course we want to maintain this
22:05category at around 10%.
22:07We don't want that.
22:08This is a wastebasket in which
22:10you put all the cases and all the
22:13diagnosis for which you don't
22:14you you don't know what to do.
22:16The new plastic category is super
22:19classified has new plastic benign
22:22which is used for the classic
22:24example Harplyomorphic adenoma.
22:26You can see here myopitelial
22:28component in this condomix.
22:29So it does traumal material warting
22:32tumor lymphoma and Schwannoma.
22:34This is a warting in which you
22:36have the Oncocity cells in this
22:38dirty background and of course
22:41inflammatory component Risk of the
22:43risk of malignancy is lower than 3%
22:45in the 1st edition was lower than 5%.
22:49We add also these other category
22:52sample and certain malignant potential
22:54when we use this and the definition
22:56here is diagnostic of a neoplast.
22:59So we are sure that the sample
23:01is diagnostic of a neoplast.
23:02By the way a diagnosis of a
23:05specific entity cannot be made
23:07due to the nature of the lesion.
23:09So we are not able to define capsule
23:12and vascular invasion on cytology,
23:14but also sometimes due to the affine so
23:17that a malignant cannot be excluded,
23:21the risk of neoplasm is a malignancy.
23:23Sorry, is at around 35%.
23:25In the 1st edition was 26 and we
23:29included the many benign anti
23:31dysclomorphic adenoma with the
23:33squamous metaplasia,
23:34cellular pleomorphic adenoma,
23:36myopia, lioma,
23:37basal cell adenoma and so on.
23:41You can see here three different characters
23:43performed by Peter Salos the amazing
23:45Peter Salos in Doctor Strangelove.
23:47As we had different types of hub,
23:50the same sample in the second edition
23:53we have a sub classification of
23:56sample into Basaloid orchocytic
23:59clear cell features which were
24:01identical to the 1st edition.
24:02But we added mix it the features
24:05because it's not it's not always
24:08the white or black and we have this
24:11different shades of Gray and can
24:13be and a mixture of the different
24:16mentioning the pattern.
24:17Just an example in the upper left you
24:19have a typical basaloid appearance
24:21in which you have these are Fazard,
24:24the organization of cells basaloid
24:26with the scan to cytoplasm.
24:29In the upper right you can see
24:32an oncocytic appearance
24:33of this sample. This was a myopithelioma
24:36on estology and in the bottom you can
24:39see this cluster with this delicate
24:41and very granular and clear cytoplasm.
24:43This was an acinic cell carcinoma
24:47on estology, but it's not only
24:49important for the sample to sub
24:51classify the different type of cells,
24:53but for each of them is also important
24:55to sub classify the differences in the
24:58background because it is associated with
25:01different entities and we did the for
25:03each of them there's a sub classification.
25:06So Oncitic and you can see we
25:08might have a cystic background,
25:11a mucinous background,
25:12blood on a specific background.
25:14And for each of them we define all two
25:18possible entities which are defined with
25:20the within details in of course the
25:24Atlas with criteria with explanatory nodes,
25:27the granular and baccalais cytoplasts which
25:29is mostly associated with malignantitis
25:32and approachable focal nuclear atibia,
25:34again malignant antitis.
25:36We did the same for Basaloid and you might
25:40say that in the in the Basaloid pattern
25:43we might have a fibrillary stromal component,
25:45eyeline mix it and scan
25:48to no stromal component.
25:50And for each of them we have
25:53different type of Antidis.
25:56By the way.
25:56Generally speaking for an F&amp;A to be
25:59competitive as a diagnostic test.
26:01This is not only for salivary,
26:02this is in general we strive to
26:05shift cases from the indeterminate
26:08category to benign or malignant.
26:11For instance,
26:11this was what I mentioned in this morning.
26:14If we have a case like this in
26:15which we have this delicate for
26:18granular cytoplasm and this cluster,
26:20it's clear that this this is neoplastic
26:23but without the support of immuno,
26:26we cannot go farther.
26:27But if we perform immuno and we see that
26:30this is dog one and no one positive,
26:33but we can shift from a sample to
26:36the definition directly on cytology
26:39but acidic cell carcinoma.
26:41Let's analyze the bad or if you prefer
26:45something like the Eden apple by Margaretta.
26:48This here is a part of the
26:51indeterminate categories.
26:51With AUS and sample,
26:53the risk of neoplasm is at around 83%.
26:56We emphasize the important role of
27:00ancillary technique so that we can
27:02shift to the malignant category
27:04if we have enough material.
27:07I want to do a differentiation.
27:09So AUS.
27:10We are saying that the the the
27:12keyword is limitations and in front
27:15of an AUS we are not sure if this
27:18is neoplastic or reactive in sample.
27:21We are sure that the deletion is
27:23neoplastic but we are not able to say
27:26if it is benign or a malignant neoplasm.
27:29But a Sunnybury gland sample in which
27:32we use the diagnosis of suspicious
27:35for malignant means that we have some
27:39of of the criteria for a diagnosis
27:42of malignancy but not the whole.
27:45So we are not completely confident
27:47in a diagnosis or malignancy.
27:50This is a you know the the moving from
27:53AUS to suspicious for malignancy.
27:56We sub classify into of course
27:58suspicious for a primary
28:00cerevaricular malignancy,
28:02metastasis and lymphoma because
28:04it's important for the management.
28:06Some example you can see few clusters
28:09are typically malignant but not enough
28:12for any conclusion or some clusters in
28:15which we have some artifact And of course
28:18we recognize that there are some Atiba,
28:20but we cannot be completely confident
28:22in a definitive diagnosis or malignancy
28:25also because I would like to remember
28:27that a diagnosis or malignancy is
28:30associated with a more aggressive treatment.
28:32So you have to be sure of that what
28:35you are saying what you're seeing on
28:37cytology is is correct and is the right
28:40diagnosis and of course you you have you,
28:43you have to have enough
28:45criteria for this diagnosis.
28:47Some other example of suspicious on the
28:49upper right that you see this delicate
28:52and salt and pepper appearance but
28:54just in one cluster we are not able
28:57to apply the also the immuno or in the
28:59bottom in which we have this population
29:02of this cohesive typical cells looks
29:05like a lymphoproliferative disorder,
29:07but again not enough
29:08material for flow cytometry.
29:10Or also here on the right you can see
29:13in favor and suspicious for lymphoma,
29:15lymphoproliferative disorder,
29:17but we need to be sure to immunophenotyping
29:21and sometimes we do not have enough material.
29:24Another example is this few cells
29:27in which you see there's a mucinous
29:29component in the cytoplasts and this
29:32was on Histology and Mac but not a lot
29:35of the clusters or this in which you
29:38have this delicate population of cells,
29:40just a few clusters with some heart effect,
29:43some blood not enough for for anything.
29:46So it's better if you stay with
29:48us a speechless for malignancy.
29:50Another possibility here is if you
29:52use if you define the specific
29:55criteria for an entity.
29:56In this case you can see the criteria for
29:59epidermoid appearance of the cluster and
30:02on the right mucus of producing cells.
30:05But again,
30:06not enough with only this.
30:08The two cluster to say this is a Mac,
30:11so it's better to use suspicious
30:14of for malignancy favoring a Mac.
30:16Also these other examples,
30:18this was the only the only few
30:21clusters in these pictures that are
30:23of course as you can see highly
30:26suggestive for adenocystic carcinoma
30:28because of these translucent material,
30:29the best alloyed appearance of the cells.
30:32But again for this so tough diagnosis
30:36you cannot base the, the,
30:39the,
30:39the record only on there's a few
30:42clusters not they are not not enough.
30:45Let's go to the Hagley or the
30:47inhabitants of an apple by Madrid.
30:51This is the the, the,
30:52the category of malignant is defined
30:54when we have all the criteria,
30:56isn't the first maybe the adhesives the
30:59category because we have samples in which
31:02we recognize the criteria for malignancy.
31:05We try to super classify when possible
31:08into the different types of course
31:10and also degrades because again it's
31:12important for the management and also
31:15it's important to recognize if this is
31:17a lymphoma of coma or a metastasis.
31:20The risk of malignancy now
31:22is higher than 9080%.
31:23In the 1st edition was higher than 90%.
31:26This is the declassification.
31:29We have an introduction and then a detailed
31:31discussion of all the different entities.
31:33You can see in the upper part is a liquid
31:37based ontology of an epimycopelial.
31:39You can recognize the luminal basaloid and
31:42the abnormal myopelial clear cell component,
31:45the acetic cell carcinoma,
31:47with this granular appearance
31:49in the upper right,
31:50the Mac in the left bottom with the
31:54epitelial cells and mucus producing
31:56cells and the typical appearance of hub
32:00eyeline are cellular globals so that you
32:04have surrounded by cells back-to-back
32:06that you have in adenocystic carcinoma.
32:09Some example from the Atlas.
32:11So this is an ascenesal carcinoma in
32:14which you can recognize the granular
32:17abundant cytoplasm and also you can
32:20see the very low nuclear cytoplasm
32:22ratio of some nucleolide And of course
32:25if you are lucky enough to have a
32:28material you can perform immunostate.
32:30In some cases you can also recognize
32:33the cymogen granols has in this picture,
32:35but usually positivity for dark
32:38one and nor one.
32:39This is an example of a secretary
32:42carcinoma in which we have this low grade,
32:44the vesicular nuclear high,
32:46the back related cytoplasm and some
32:49prominent nucleoli and again if you have
32:52material and you can perform cellblock,
32:55mammoglobulin and aspirin Android
32:58they are positive.
33:00This is an example of a low grade Mac
33:02in which you have a combination of the
33:05epidermoid cells with a really well
33:08defined cytoplans border and there's
33:11an oncositoid appearance intermingled
33:13with this mucosa producing the cells.
33:16So,
33:17but we have to remember that we have
33:19also the I grade the Mac in which we
33:22have this really highly pleomorphic
33:24mostly squamoid and squamous cells
33:27and if we are lucky enough we can
33:31recognize this mucinous component.
33:32Sometimes this is not possible,
33:34especially also on Histology.
33:36So you can recognize with pass and pass
33:40the the of the mucosa producing component.
33:45This is an example of salivary duct
33:47carcinoma in which we have usually
33:50isolated cells or Synthesia like
33:52cluster usually 3 dimensional with
33:55well defined cell borders with the
33:58prominent eccentrically located the
34:00nuclear high oncocitoid appearance
34:02of the cytoplasm.
34:03Based on morphology alone you cannot say
34:06that this is a salivary duct carcinoma.
34:09You can define this as an eye
34:12grade carcinoma.
34:12It's only the support part of immuno
34:15and the positivity which is specific
34:17for androgen receptor that make
34:19you the possibility to put this
34:22in a definitive diagnosis of
34:25SDC. You have of course also
34:27necrotic and mitotic component,
34:29it's an high grade carcinoma
34:30and other other two example have
34:32adenoid cystic in which you have
34:34the tubular pattern, very nice.
34:36The most commonly seen of the crib
34:39reform in which we have these highline
34:42translucent globules with cells
34:44surrounding around or the solid pattern
34:46which is the most tricky because it
34:49might resemble of course a vessel
34:52cell adenoma versus vessel cell,
34:54mostly carcin.
34:55And this is also another typical
34:58example of the crib reform pattern
35:00in the crib reform adenoid,
35:03the cystic carcinoma.
35:04But as mentioned it today I
35:06would like to remember that we
35:08might have also metastasis,
35:09the most commonly seen
35:11however metastatic Melanoma.
35:12As you can see in the upper right you
35:15have this difference appearances of
35:17the cells nucleus with inclusions,
35:20evidence of pigment in the
35:22cytopolis or in the background
35:24binoculated cells cells and also
35:27of course metastatic squamous cell
35:29carcinoma in which we have this
35:32orangiophilic and dance appearance
35:34of the cytoplasm necrotic component.
35:37Irregular cells and nuclei.
35:40This keratotic orangiophilic
35:42cells the the squamous cell
35:45carcinoma of the salivary gland.
35:46It's exceptionally rave.
35:48So when you have a squamous component,
35:50the first differential that you have
35:52to put to have the I grade Mac try
35:55to recognize if this is an I grade
35:58Mac with this extensive as squamous
36:00component and metastatic localization,
36:03especially from the adenac that also
36:05metastatic from another side and then
36:08as an as a diagnosis of exclusion
36:10when you haven't find anything.
36:12But it's almost impossible.
36:14Think about a primary squamous carcinoma.
36:18It's important to to grade in
36:20onsettology also because this will
36:22influence the extent of surgery.
36:24So it's an important information for the
36:28clinicians in term of radical resection,
36:31limited resection,
36:32negative session,
36:33facial nerve of course sacrifice.
36:36We published it in 2010 and 20 this paper,
36:40including 66 digitized cases
36:42of the livery carcinoma.
36:45The cases were reviewed by a panel
36:47of experience in the cytopathology.
36:4919 You can see that the overall
36:52grading accuracy was 90%.
36:54We wanted to see the ability of F and
36:57A to distinguish low grade versus I
37:00grade 20 I 90% and 808088 point 3%
37:06impossible for the indeterminate for
37:09the intermediate grade and the best
37:12results of course were obtained with Mac.
37:15So we concluded that that cases should
37:18not be graded one in the terminate.
37:22We also discussed it about this
37:24is Doctor Farkin and I about the
37:26role of ancillary technique if
37:28we have to stay with the chapter
37:31or we're changing something.
37:33We decided that according to the
37:36reason to also new changes in
37:38the genetic alterations we wanted
37:41to maintain the chapter.
37:43Mostly there is the evidence
37:44by the literature.
37:46This is just one of the example that
37:48all the possible ancillary techniques
37:51can be performed with the feasible
37:54and reliable results on all the
37:58different psychological material.
38:00And this is the summary of the chapter
38:03in which we have an introduction,
38:05then a description about the
38:07material and methods, the special
38:09stains but also immunocytochemistry
38:11in the different type of lesions.
38:14And of course the role of translocation and
38:18fusional oncogenes are in salivary tumors.
38:21But also the role of Fisher PCR
38:24next generation sequencing and flow
38:26cytometry in the upper part is music
38:29harming in the Mac in the middle.
38:31Here's a plan,
38:32one nuclear expression and in the
38:34bottom is ACD 117 in a cluster from
38:38another noise cystic carcinom.
38:40And these are the tables about the
38:42immuno for the different patterns.
38:44So they are all included of course
38:46in the chapter and in the second edition.
38:48And you can see we classified the
38:51oncocytic pattern including benign and
38:54malignant antidisal warting oncocytoma,
38:56acinic cell carcinoma secretory Mac,
38:59salivary Dr.
39:00and all the possible immunomarkers
39:02with positivity and negativity.
39:04For the basaloid we did the
39:07same gliomorphic adenoma,
39:08basal cellular denomin Sonoma,
39:10adenoid myopetalioma and
39:12Myopetalia carcinoma, AP,
39:14myopetalia and polymorphous
39:16adenocarcinoma and all the
39:18possible positivity and negativity.
39:21The same for clear cell features myopia,
39:23lioma, myopia carcinoma,
39:25AP, myopia carcinoma,
39:27acinic Mac and also the hyalinizing clear
39:31cell carcinoma and the different markers.
39:34And of course also a table for
39:38the metastatic localization and
39:40the possible site of the origin.
39:43This is a table concerning the genetic
39:45alterations and you can see that these
39:48are associated with different type of tumors,
39:51not only malignant tumors and we might have
39:54different of them rearrangement of fusion,
39:57some mutations,
39:58amplifications.
39:58And when you look at the percentage of cases,
40:02we we have some example of very high
40:07percentage including of course in psychotic
40:10carcinoma 100% for the different ETV
40:146 and TRT three and not only fusion.
40:19So in conclusion,
40:20we can say that the F and A has a very high
40:24diagnostic accuracy in salivary cytology.
40:26This is a regardless of the classification
40:29system and the Milan system.
40:31By the way,
40:32the use of a classification system,
40:34in this case the Milan because
40:36it's the unique classification that
40:38we have for salivary may offer
40:41information for the management.
40:43So it's a practical classification
40:45system in which we put the deletion site
40:49with risk of malignancy and strategies
40:51we had of course improved the relevance.
40:54So we are very happy for
40:56that fundamental system,
40:57The Who and Dorset,
40:59the melon system,
41:00but mostly the American Society
41:02of Clinical Oncology.
41:04The 2nd edition revised of course
41:06the criteria the risk of malignancy
41:09for each of them based mostly on the
41:13200 publications and meta analysis.
41:16And in this regard I have to say that
41:18the major job for meta analysis and
41:21reviewers reviewer reviews was done
41:23by Doctor Balacha and his team in Upenn.
41:26So we are really thankful to the amazing
41:29job that Zuber did for the new risk
41:33of home malignancy in the second edition.
41:36So is this again the high
41:38noon of salivary cytology?
41:40So the Milan system is against
41:42the classical cytology.
41:43Of course it is not also in this edition,
41:46because we didn't change anything in the
41:49classical evaluation of salivary cytology.
41:51We didn't have any new entity,
41:54any new feature,
41:56any new morphological something.
41:58We only revise and refine some criteria.
42:03Making possible to have these
42:05entities is put into categories,
42:08specific categories for and for
42:10each of them we have a risk of
42:13malignancy and the management.
42:14So it's a practical classification system
42:17as of course it is also the Bethesda,
42:20the and all the other do I hand.
42:22All the other classification systems are
42:25the same meaning and the same purpose.
42:29I would like to conclude with
42:30these two pictures.
42:30One here's the party for the publication.
42:33I have the first Atlas during the news
42:35Cup 2000 than any team in Vancouver.
42:37This in these are pictures when we
42:40receive the the the hard copy of
42:42the 2nd edition Doctor Faquin and
42:44I and the harder Associate editors
42:46and really would like to thank all
42:49of you for having been here and for
42:52having invited me here and thank you.
42:54Thank you so much and if you have any
42:57question I'm open to to discuss with you.
43:00Thank you.
43:08Thank you for this. Fantastic.
43:11Oh, thank you and all this can
43:13be. Oh yes, I'm really,
43:16I'm really keen of that. Yeah,
43:17I've seen most of them. So I
43:22do have a question. I mean,
43:24since you also got this
43:29Once Upon a time when I was there
43:33was a lot of rest happening and
43:36then it just fell out of the way
43:39and this goes now the standard of
43:43here is a poor biopsy looking.
43:45Do you see that happening in salivary
43:50tumors like cold wide oxy or something
43:53like that replacing the epine?
43:57Because all those categories I find
44:01I find it very challenging because
44:04the limitation is a few clusters,
44:07they may be just cluster or maybe just
44:14in my institution,
44:15which is the same approach that also
44:19Doctor Faquin has in mass General
44:22for the major salivary gland,
44:24I always do an FNA.
44:27So usually core biopsy are done
44:29only for the minor salivary gland
44:31because for them it's more difficult.
44:34But in any possible case in which I
44:37can perform a fine needle aspiration,
44:40I try to go with a fine needle aspiration.
44:43If you have a conventional in,
44:45like in our case liquid base or cytology,
44:49we prepare a cell almost in any occasion a
44:55cell block from the from the liquid base.
44:58Of course there are some cases in
45:00which we do not have enough material,
45:02but in the majority of cases it's
45:06not so bad and we can, you know,
45:09work on lands with ancillary
45:10technique on them.
45:12So I don't,
45:13I don't have a big experience with
45:15core biopsy especially on priority
45:18to someone our experience is mostly
45:21psychology and they prefer to do to
45:24do to do that because there is a big
45:27clinic of salivary my institution now.
45:30So I don't have for the minor,
45:32minor salivary gland because it's more
45:34difficult that they they do some of them.
45:36So here in US in our
45:41practice, the poor biopsy or the F
45:44and A is done by the radiologist who
45:48is doing the ultrasound examination
45:51and the cores come to me and
45:55the F and A is the psychology.
45:58And of course it's just so much
46:02easier to make a diagnosis.
46:04Yes, well in in, in our institution
46:08and we we don't do that.
46:10But you know, even if the same because
46:14we have an organization in which
46:16the same person does psychology,
46:19mystology. So the biopsy and the
46:21psychology when they are,
46:22I've always seen the same person which is me.
46:24So I have I have the same at the
46:28same point almost at the same point
46:30and both of them and I I can check
46:33and I can see if there is a biopsy
46:35or not In in in the past we went
46:38to the to do the to perform the
46:41F and A at the beginning.
46:43I I personally want but you know it's
46:45impossible now so we had a resident
46:50that sometimes when there are some
46:53critical cases goes usually we
46:56taught the hand and neck surgeon.
47:00So to do the the F and AI have
47:03to say that at the beginning was
47:05a disaster a lot of blood had a
47:08lot of non diagnostic with time
47:10and you know being closer sending
47:14the resident to explain is going
47:17better absolutely better and you
47:19know they're they are successful in
47:21what they are doing I have to say.
47:23So yeah it's
47:30a great talk. You know it's a lot very
47:32beautiful pictures movies and yeah
47:36like the the the thought I you must
47:39have not see any of those movies.
47:42So my my question
47:46to you, you know you you you mentioned
47:48you know in the category of medication
47:50diagnosis people intended to feel more
47:52specific or even breeding their malignance.
47:55They talk about low grade versus high grades,
47:59you know but you know this is the
48:03you know it's probably easier for
48:05like a type tumor like you have to
48:09have you know slow grade, high grade.
48:14But for some of the tumors I I kind
48:18of you know what's going to put
48:20a category like a hydroid cystic
48:23are you going to put a low grade
48:26adenoid I grade slowly I grade adenocystic
48:30carcinoma I grade I agree yeah.
48:33So because you know we consistent you
48:38know we mean
48:40you know we you know make it.
48:41I mean the our our idea is that
48:43you know when you it's not on it's
48:46not specifically about low grade
48:48but it's mostly about high grade.
48:50So if you see something which is
48:52really high grade just call hit
48:55high grade regardless if you're
48:57able to do a further definition of
49:01it because you have immuno because
49:03you can do the molecular and so on.
49:06But if you if you recognize that this is
49:10an I grade the carcinoma for instance.
49:11I'm discussing about carcinoma just
49:14you know variety it because you know
49:17for the clinicians is it's important
49:19to know that this is an I grade.
49:21Yeah. So you know you really you know the
49:29secretary is for instance low grade
49:31secretary is not is low grade.
49:33The majority of basinic are not high
49:36grade unless you have the the the high
49:39grade differentiation and you see.
49:40So it's not so important
49:43to to write low grade.
49:45It's more important to to write high
49:48grade when you see something which
49:50is like grade like a high grade
49:53Mac or all the all the high grade.
49:57This was our meaning for this in
50:00for this purpose for the management.
50:03I
50:11have a question. I have
50:18no question the molecular
50:21ancillary testing in your practice
50:25not allowed especially because in
50:27my institution we had the molecular
50:30in my institution now was more
50:33on the we are on the 4th floor,
50:35on the third floor in general pathology.
50:38So really I tried to do to reach a
50:43diagnosis and to make a diagnosis
50:46with morphology with the immuno as
50:49a first approach and then in some
50:52specific and selected cases in
50:54which I'm not able and I want that
50:56or they ask a better definition,
50:59specific definition I sent to the molecular.
51:03But you know,
51:04it's not in all the cases because
51:06we do not it's not available
51:11in a normal way.
51:13Immune or noise is easier.
51:14So we can do on the cell block.
51:17So for instance,
51:18when I'm when I'm in doubt on morphology,
51:21the first thing that I do is the cell block.
51:25In this way I can realize the morphology,
51:27I can realize all the things
51:29that are in doubt.
51:31And then based on this I decide
51:33which type of immune.
51:36Another thing why why is there for thyroid
51:40that we only liquid based psychology?
51:43Because we have many and it's impossible
51:45to do conventional and the liquid based
51:48psychology for salivary psychology,
51:50despite the fact that we could have done
51:53only on the liquid based psychology,
51:55I asked them to do liquid
51:58and the conventional.
51:59Because salivary psychology differently
52:02from other type of psychology is for
52:06the diagnosis is really important
52:08as reported in the table to define
52:11this else but also the background,
52:14the different the differences in the
52:16background if it is eyeline if it
52:18is musing us. If it is more cystic.
52:22It's really very important in focusing
52:27on the differential diagnosis
52:29and on liquid based psychology.
52:31I'm I'm better in recognizing
52:36the nuclear details,
52:37but the background details are much
52:41better defined in conventional psychology.
52:44So I need both and I don't.
52:46I don't want to to to move only
52:48on the liquid based ethology.
52:50By the way,
52:51there is a very nice paper published
52:54about liquid based ethology in
52:56Salivary for a special issue of
52:58ACTA psychological some years ago.
53:01The first author is Rarick with
53:05our and the and Co working with
53:08the Claire Michael.
53:09It's a very nice paper about water
53:11liquid based ontology and all the
53:14different entities and criteria in
53:15saliva relations. Very nice in my opinion.
53:18Thank you.
53:29Thank you so much.