Pathologic Anatomy: Metaplasia, Dysplasia, and Squamous Cell Carcinoma

Guglielmo Pernice Maurilio Ponzoni Pathologic Anatomy

16/10/2023

Introduction to the Course

The course is intense, and we will have to study a lot as we will cover a lot of notions. What is expected from us is active class participation. Pathology is much wider than what we will cover during our studies, the concepts that we are requested to learn are the basis for becoming a general practitioner and an excellent MD. We have to acquire the methods and knowledge to understand pathologists' words correctly. Most importantly, we must understand and interpret the reports made by pathologists to correctly cure our patients and avoid making a mess.

At the end of the course, we will have some sessions that will enable us to look at some histological slides through digital pathology. This will allow us to look at the images more in- depth. The histopathological slide's aim is to combine the theory learned during the course with the morphological data seen in real life.

Suggestions: as already said the course is very dense therefore the professor advises us to start studying right away, and avoid the use of short resumes, if we try to study everything before the exam from his experience, he's sure we will most likely fail.

In this course, we will have a sort of internal medicine applied to morphology so we will deal with several diseases coming from different specialties such as cardiovascular pathology or breast pathology. Diseases do not know books so we must make connections between information and interpret the data by analyzing all the possible cases.

In the course we will also have a review of the most important features at the microscope so, for example, when we study the squamous cell carcinoma of the tongue, we will see some images that show how it appears and how it is made.

The professor offers a portion of his Friday afternoon just for fun to sit down at the microscope for people interested in going deeper into pathology. He mostly covers hematopathology, so it is very rare to see other branches of the discipline. He suggested coming if we are interested after we took and passed the exam as we would see too many exceptions to the rules, and this may confuse us when preparing the exam.

We must refer to the syllabus to have information about the exam.

The book is "Robbins BASIC PATHOLOGY", it should be used along the slides of the lessons.

Exam Structure

The exam is split into 2 portions: a written part and an oral one. The written part is composed of 20 multiple-choice questions. How does it work? We first take the written part which will be corrected the same day to allow us to take the oral part soon after. The role of the written exam is neither to have a skimming and stop people from taking the oral part nor to contribute to the oral part. If we score 20/20 and we are not able to answer the first oral question we will be sent home. At the same time, even if we score 1/20, we can still take the oral exam and maybe pass it (it will be harder than if we get 20/20 as the questions will go deeper). The role of the written exam is to give the professors an idea of our overall preparation.

Oral Exam Rules

Oral exam rules: there is a list of different topics from the syllabus which are numbered progressively. We will choose the topic by randomly picking up a number, like a lottery. Each number has a particular topic, if we can't talk about the topic we picked we fail the exam. No histopathological slides will be asked during the exam, the ones that will be covered in the lessons are just for our understanding and culture.

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Professors of the Course

• Professor Maurilio Ponzoni
• Professor Pietro Luigi Poliani, Neuropathologist.
• Professor Massimo Loda
• Professor Maurizio Colecchia, soft tissue tumors and part of pulmonary pathology.
• Doctor Francesca Sanvito, an expert in cardiovascular pathology
• Professor Federica Pedica, pancreatic, liver, and breast pathology.
• Doctor Lucia Bongiovanni

The language used by pathologists is what we need to know and understand from this course.

** Hematopathology + dermatopathology will be discussed in the second semester, while GI pathology will be covered in the 5th year.

Recap on Last Pathology Lesson

Metaplasia and Dysplasia Distinction

Q: Are we able to distinguish between metaplasia and dysplasia ? Which is the main difference? A: Reversibility for metaplasia Yes, but keep in mind that the roild dysplasia is still reversible therefore dysplasia is not 100% irreversible. While when we deal with the moderate and severe those aren't reversible.

Q: What is the actual main difference between the two? A: The growth is gosordered in dysplasia whereas in metaplasia it is ordered as it is an adaptive responss (the tissue needs to adapt to damage for example). In dysplasia this change is random as it isn't meant to adapt a tissue to a specific stimulus. In metaplasia, we see one cell type reversibly switching to another cell type.

Q: What are the cytological details that may worsen and suggest that it is not an adaptive change but an irregular disordered growth? What is pieomorphism? A: Pleomorphism denotes the variability in the size snape, andtexture of cells and/or nuclei in a micro-environmental area.

Q: At the nuclear level what do we expect to see? dysplasia: A: We expect to see a hyperchromatic nucleus and coss of polarity, these features define a tissue as dysplastic rather than metaplastic

Q: What is the relationship between dysplasia and metaplasia? A: We cannot have metaplasia on top of dysplasia, but we can have dysplasia due to metaplasia. But this is not a rule, we have some cases such as Barret esophagus in which we develop dysplasia on top of metaplasia. There aren't many other situations such as this.

Choristoma Definition

Q: What is a choristomay A: The occurrence of normal components of a tissue in a non-native tissue (normal cells that are not supposed to be in that tissue)

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Choristoma vs Hamartoma

Q: What is the difference between choristoma and hamartoma? A: In a hamartom, we have an occurrence of physiological celis in a tissue to form an irregular lesion (those cells are supposed to be there)

Head and Neck Pathology

Structures of the Head and Neck Region

First of all, which are the structures that belong to the head and neck region?

• Oral cavity
• Upper airways
• Ears
• Neck structures
• Salivary glands

For simplicity, the thyroid will be covered during the endocrine portion of the course.

Oral Cavity Disorders

Very often the oral cavity is the site of many disorders which are mainly inflammatory, mostly chronic inflammatory states. These inflammation targets 2 structures:

• the cingiva and
• the periodontium.

The inflammations that target these 2 sites are called respectively gingivitis and periodontitis.

The periodontium is adigament that keeps the feetb within the alveolar cavity of the maxillary and mandibular bones

Q: When we look at chronic inflammation under the microscope which cells do we expect to see? A: Lymphocytes and plasma cells, not granulocytes.

Inflammatory/Reactive Lesions

Irritation Fibroma

Then we have a series of particular inflammatory/reactive lesions: Irritation fibroma the first one arises in people who use the dental plate and are subject to a sort of mechanical damage to the oral mucosa. It is called irritation fibroma, and it is caused by a chronic inflammatory infiltrate particularly due to an enrichment of plasma cells.

Q: It is called fibroma so what type of cells do we expect to see along with plasma cells? A: Fibroblast

Figura 16.2 Fibroma. Nodulo liscio, roseo, esofitico della mucosa orale.

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Pyogenic Granuloma

Pyogenic granuloma This lesion may suggest from the name a presence of pus but in this case, it is not part of it. We can find the lesion in patients of all ages but usually, it targets the gingiva of children, young adults, and pregnant patients.

Q: What could be the reason for the presence of the condition in pregnant women?

Figura 16.3 Granuloma piogenico. Massa eritematosa, emorragica ed esofitica a partenza dalla mucosa gengivale.

A: Hormone imbalance, much more than in any other physiological phase of a woman's life. It is not formally proven but some speculations support this theory.

How can we recognize the pyogenic granuloma? We can see on the gingiva a nodule which is increased in size and is ourpie to red. Why this range of color? Because there are a lot of vessels; and when we have dilated vessels or engulfed vessels by erythrocytes, we have a reddish appearance.

Q: If a patient comes to our office after he's been diagnosed with pyogenic granuloma and asks us what he should do or what will happen to him what can we say? A: We should explain to the patient that there's no need to worry as usually they are reversible and they spontaneously regress

TheRegression is important and should be monitored because if that doesn't happen dense fibrosis may be developed as a consequence. Dense fibrosis may undergo osseous metaplasia, a further pathological adaptive response, and lead to the deposition of osseous tissue where there shouldn't be any. To resolve the problem in the absence of a regression the best option is to remove the esion surgically.

On the right, we can see how it is made, it has a sort of polypoid appearance (image on the top). On the sides, we see a squamous epithelium with a middle cauliflower-like structure. They are small, around 1cm. if we cut them and analyze them histologically, we can see some nodules within the dermis. At higher magnification, we see the appearance of empty spaces that contain ed cells. The outline of these vessels is not round like we expect but ratherdrregulan

Q: What is granulation tissue in inflammation?

PYOGENIC GRANULOMA 'young vessels'

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A: It is the situation in which we are starting to restore the original tissue through a transitory structure. During this phase, we can find a young connective tissue enriched with newly formed vessel9. So, the granulation tissue is an early repair attempt.

Beyond vessels you will see also some cells that are granulocytes, they don't form a dense population, hence you can't define it pus. The name of the disease is misleading as there is no pus. It is very difficult to find a pyogenic granuloma outside the oral cavity, but we can find them under the toes sometimes.

Oral Cavity Infections

infections: Which are the most frequent infectious agents in the oral cavity? Poor hygiene could bring infections, but it is not the right answer. Which are the infectious players?

• Herpes labiale (HSV) and
• Candida.

Candida is very common in immunosuppressed patients. Streptococcus is a very aggressive bacteria that usually targets the consils, it is possible to have an infection due to this bacterium, but it is not one of the main causes. Bacteria are not the main candidates for inflammations of the oral cavity. Smoking is a mediator of infections due to suppressed immune activity.

When we see a patient with an oral cavity lesion, we should always consider that the oral cavity may be the targetof a systemic disease. We can consider the oral cavity as a sort of sentinel to investigate systemic disorders.

Hairy Leukoplakia

dairy leukoplakia Hairy leukoplakia has a particular anatomical site of development in the oral cavity: the border of the tongue. If we see a lesion that resembles the hairy leukoplakia but it is on the tip of the tongue or on the gingiva we can be sure that that is not it.

It is an EBv-associated disorder, EBV belongs to the herpes virus family together with herpes virus type 8 and cytomegalovirus. We encounter the occurrence of EBV in groups of people who share the immunodeficiency condition, especially acquired immunodeficiency. Patients with HIV are immunocompromised, and they usually develop opportunistic infections.

develop infections

Is EBV commonly diffused or hard to get infected by? What is the percentage of expected people infected by EBV in our classroom? About 35-40%. It is a sort ofinfluenza-like infection. Immunocompromised hosts, that develop a new EBV infection, may experience stronger effects due to this inflammation.

Immunodeficiency Risk Factors

Who's at risk of developing immunodeficiency?

• Acquired immunodeficiency. Some classes of patients are more prone to developing immunodeficiency as it can be acquired, it isn't always congenital. This is an aspect that must be taken into account when curing patients.
• Patients infected by HIV+
• Any satient with a tumor has also some degree of immunodeficiency, if we give them therapy, such as radiotherapy the chance of developing infections increases.

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