Pathology Grand Rounds, March 21, 2024: Esther Diana Rossi, MD, PhD
April 03, 2024Information
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."
ID11534
To CiteDCA Citation Guide
- 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&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&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.