As pathology is a largely unknown field in medicine, we are glad that Dr José Cândido Xavier Jr., a specialist in surgical, dermato- and cytopathology, agreed to shed light on “The role of a pathologist in diagnosis and treatment”. This is the third part of our series.
Pathology is a varied medical field. As previously mentioned in our series, medicine is like a tree, in which the roots are the basic sciences (physiology, genetics, cellular biology, anatomy, histology, and so on), and the twigs are the medical specialties (dermatology, gynecology, urology, gastroenterology, hematology, etc.). The sub-specialties of pathology provide the connection between the trunk and the twigs. For example, dermatopathology connects general pathology with clinical dermatology. Dermatopathologists study diseases related to the skin, including abnormal growth of tissue, infections, inflammation, bullous conditions, autoimmune diseases, and pathophysiological processes like aging.
In the same way, hematopathology studies diseases and processes related to blood cells, bone marrow, the spleen, and lymph nodes. This sub-specialty also deals with lymphomas outside of lymph nodes in tissue like skin, mucosa, and other organs. There are many different sub-areas of pathology, including gynecopathology, ocular pathology, head and neck pathology, bone and soft tissue pathology, cytopathology, and others. Sub-specialization allows pathologists to become experts in a specific area.
Considering all pathological fields, cytopathology deserves a specific explanation. Cytopathology does not focus on one organ or system. Cytopathologists analyze smears, not formalin-fixed and paraffin-embedded samples. They do not examine the tissue itself; instead, they study cells prepared on slides. Dr. Papanicolaou famously studied the cytology of the uterine cervix in the last century. The Pap smear or Pap test, which is a test for cervical cancer, is named after him.
In recent decades, some protocols were developed to standardize the cytopathological findings and reports for many materials (e.g., the Bethesda system for thyroid cytopathology, the Milan system for salivary gland cytopathology, the Paris system for urinary cytopathology, etc.). Cytological specimens can be collected with a swab, cytobrush, or fine needle aspiration.
To illustrate the breadth of pathology, let’s take the example of breast cancer because it is one of the most widespread and fatal cancers worldwide. Can you imagine that the most recent World Health Organization book (part of a series called the WHO Blue Books) about breast tumor classification runs more than 300 pages and lists more than 70 distinct conditions and tumors from malignant to benign? Medicine and pathology are constantly evolving. Over time, researchers uncover findings that allow precise tumor classification, and new entities are discovered that make cancer classification a dynamic process. Without exaggeration, every human tissue can generate an abnormal growth of tissue; if there are cells, there is a chance of cancer.
From epidemiological studies, we can infer that some cancers are age-related. For example, nephroblastoma, a malignant kidney tumor, most frequently affects children. Prostate cancer, by contrast, usually occurs in the 50s and most frequently after 60 years of age. So, pathology can help guide public health policies toward high-risk people. Even though most cancers have a familial relationship (meaning that if my father had prostate cancer, I have a higher chance of prostate cancer than the ordinary population), most malignant tumors are not related with genetic heritage syndromes (germinative mutation).
Some tumors are associated with risk factors; for example, smoking is related to lung and oral cancer. We also know that there is a relationship between some viruses (like human papillomavirus and Epstein-Barr virus) and cancer. Sun exposure is a primary cause of skin cancer.
Although the understanding of cancer is increasing, much remains to do. Most cancers have no established risk factors or causes. These gaps reinforce the importance of pathology in medicine. Despite the challenges of our specialty, our primary job is to help generate accurate diagnoses to ensure patients receive appropriate treatment and live their best lives.
As pathology is a largely unknown field in medicine, we are glad that Dr José Cândido Xavier Jr., a specialist in surgical, dermato- and cytopathology, agreed to shed light on “The role of a pathologist in diagnosis and treatment”. This is the second part of our series.
Why Is There a Need for a Pathology Report?
All cancer diagnoses require a pathology report. These reports provide critical information that guides treatment and follow-up in addition to diagnosing the tumor. To design a treatment plan, oncologists and surgeons must scrutinize the pathology report. They also take advantage of auxiliary techniques which can be applied to pathological specimens and might provide prognostic features (i.e., if the cancer is aggressive or not) and predictive features (e.g., whether a tumor has a good chance of responding to a specific drug). These features can be identified by microscopic analysis, additional immunohistochemistry techniques, or molecular examinations.
The pathology report is a medical document that consists of four parts:
- Demographic information
- Clinical information
- Macroscopic report
- Microscopic report
The first part contains the patient’s demographic information (name, date of birth, age, procedure date, and others). Nowadays, these reports often include a barcode to serve as a unique identifier.
The second part documents the clinical information, which means the general medical history of the patient. Pathology reports are based on clinical-pathological correlations. That’s why the final diagnosis considers not only what is found on the slides but also the patient’s background and medical history.
I will use a report about melanoma as an example. It is important to mention that melanoma is a malignant tumor that most frequently affects the skin and carries a poor prognosis when diagnosed in an advanced stage. Therefore, what the doctor sees through the dermoscope as well as the history of a spot or lesion (i.e., if the lesion is new or shows color changes during follow-up) are essential to a pathological diagnosis.
These findings are complemented by the macroscopic report (third part) with the gross description of the specimen. For example, considering the product of skin tumor extraction, the report includes the size of the specimen, the size of the visible tumor, its color, and the distance to the margins of the biopsy specimen.
The final and most crucial part is the microscopic report (fourth part), including the diagnosis and related features. A pathology report of a melanoma will provide a list of more than ten topics, including:
- histological subtype (i.e., if it is a variant related to sun exposure or not);
- the Breslow index (the most relevant staging parameter for melanoma), which will indicate in millimeters how deep the tumor cells in the skin are;
- possible invasion of vessels and/or nerves;
- the presence or absence of ulceration (abscess) and its extension;
- possible regression which means tumor remission (focal disappearance) at some point;
- possible brisk inflammatory infiltration around the tumor or not.
In conclusion, we can say that patients with high Breslow index and/or tumor ulceration and/or vascular invasion have poor prognoses and short overall survival.
What Does Tumor Staging Mean?
Aside from that, tumor staging is applied to pathological analyses of surgical excision (not for biopsies) and indicates how advanced the tumor is. Again, in melanoma cases, the tumor’s thickness (Breslow index) and ulceration define the tumor stage. The staging system might be based on other parameters in other organs and tumor subtypes. The stage is one reason patients with the same tumor have different disease histories. For example, consider two female patients of the same age and similar health status. If one patient has a breast tumor that is 5 cm in diameter and the other has a tumor of 1 cm, even if both tumors have the same histological and immunohistochemistry profile, the patient with a more extensive tumor has a worse prognosis, meaning a lower chance of surviving 5/10 years.
In summary, a tumor staging system classifies different patients with the same tumor at distinct levels of risk. Staging can be based on tumor size (such as in the breast) or the tissue level of involvement (such as in melanoma). However, the stage is not solely based on tumor characteristics. It also applies to lymph node status (i.e., if there is metastasis to the local lymph nodes) and metastasis to distant organs. This tumor staging system is called TNM:
- T = Tumor
- N = Node
- M = Metastasis
In this way, the staging combines pathological, clinical, and radiological information to provide an accurate profile of the tumor stage and the patients’ most likely future history.
Pathology (from Greek pathos (πάθος) = experience or suffering and -logia (-λογία) = study of) plays a significant role in modern medical diagnosis and medical research. Pathologists identify the nature of abnormal tissue and/or cells. If they find that a sample is malignant, they provide evidence to the clinician on the type of cancer, its grade and, for some cancers, the likely profile of responsiveness to certain treatments.
However, pathology is a largely unknown field in medicine. Often, pathologists are depicted as working on their own in a lab without interaction with patients or colleagues. Dr José Cândido Xavier Jr., a specialist in surgical, dermato- and cytopathology, decided that it is time to set the record straight. This is the first part of our series “The Role of a Pathologist in Diagnosis and Treatment”.
Pathologists are physicians who perform their work behind the scenes. Their specialties vary widely. Some are university professors and researchers, others might work as forensic specialists in law enforcement. Most commonly, they diagnose diseases at public or private laboratories. Basically, pathologists spend most of their time analyzing microscope slides in order to provide diagnosis, whenever it is feasible.
Sometimes the microscopic diagnosis is straightforward; however, sometimes pathologists spend hours studying unusual cases. Until a final diagnosis is made, a pathologist might ask for additional slides or use special stains that are contained in blocks of wax (see below) to identify fungi, bacteria, or substances such as amyloid. Amyloid is a type of protein. There is one disease called amyloidosis caused by its deposition in our tissue. So, it is important to recognize amyloid in the slides.
Usually, pathological diagnosis is based on a stain called Hematoxylin and Eosin (H&E). In specific situations, e.g. when looking for fungi or bacteria, pathologists additionally use the above-mentioned special stains (Alcian Blue, Silver Stain, Fite-Faraco, Mucicarmine, etc.).
There is a misconception about pathologists’ lives. Many people believe that pathologists work alone and do not interact with patients. In fact, pathologists perform procedures on patients, such as fine needle aspiration, in order to obtain tissue and cytological samples.
These may be brief interactions, but they are meaningful. Pathologists remain connected with the hospital team at all times. Interactions also occur at clinical meetings or tumor board reunions and consultations by phone calls or smartphone applications. There are some cancer-related emergencies in which the pathology report is decisive for treating patients. Patients must often wait for pathology reports to begin cancer treatments.
Even inside the laboratory, pathologists are not alone; they work in teams with other pathologists, with physician assistants, biologists, and other health professionals. Another misconception is that pathologists only diagnose cancer. In fact, they do diagnose infections and inflammatory diseases. Lupus, dermatomyositis, tuberculosis, and leprosy are just a few examples of inflammatory and infectious diseases diagnosed based on pathology reports.
A unique aspect of pathology are the step-by-step procedures to transform biopsies, surgical specimens, or body fluids into microscope slides. When samples arrive at a laboratory, they are processed according to international scientific-based guidelines. The tissue specimens are fixed in substances like formalin to aid visualization with a microscope. However, observing a raw tissue sample can provide valuable information for the final diagnosis. After processing using machines (or histology tissue processors), tissue samples can be embedded in paraffin. The blocks of wax containing the samples are sectioned and stained to make the microscopic visualization possible. Then, the microscopic interpretation of the tissue and cell morphology (analysis of the shape, structure, form, and size of cells) will start.
Pathology is the specialty sought by physicians who enjoy integrating basic science with clinical practice. Pathology is the art of seeing what appears to be invisible at first glance. Dr Richard J. Reed (1928–2021), a brilliant pathologist, once wrote that “the ability to integrate microscopic findings into a meaningful interpretation is the distinguishing characteristic of a pathologist and is the art of pathology”.
In order to become a pathologist, a new medical school graduate attends a residency that lasts 3–6 years. Nowadays, the application of artificial intelligence and virtual pathology has been helping to provide faster and more accurate diagnoses. Despite the increasing incidence of cancer, the number of pathologists worldwide is relatively small, making pathology an excellent specialty considering the quality of life and career advancement. Unfortunately, most student physicians do not discover this jewel of medicine.
Illustrations from “Fast Facts for Patients and Their Supporters: Advanced Cutaneous Squamous Cell Carcinoma” by Dr Sarah T Arron, S. Karger Publishers Limited, 2019.