Introduction to Pathology

Definition of Pathology

• Pathology is the science of suffering, according to the oldest definition from classic Greek.
• Modern pathology is the study of structural, biochemical, and functional changes in cells, tissues, and organs underlying disease.
• Pathology uses morphology, microbiology, immunology, and molecular genetics to explain disease signs and symptoms.
• A key function of pathology is providing a scientific basis for clinical care and therapy.
• Pathology serves as a bridge between basic science and clinical medicine.
• It is the scientific foundation for all of medicine.

Core Concepts of Pathology

• Etiology refers to the cause of a disease.
• Pathogenesis refers to the biochemical, molecular, and genetic mechanisms of a disease.
• Morphology refers to the structural and functional alterations in cells, tissues, and organs.
• Clinical manifestations are the clinical consequences of structural, functional, and biochemical changes.
• There is a causal progression from etiology to pathogenetic mechanisms to structural changes to clinical signs and symptoms.
• Biochemistry, molecular biology, and genetics explain pathogenesis.
• Anatomy and physiology explain morphology and morphopathology.
• Multiple causes can lead to the same morphological changes and clinical manifestations.
• The same cause may trigger different pathogenic mechanisms in different organs and tissues.
• Many diseases are multifactorial, resulting from genetic and environmental factors.

Subdivisions of Pathology

• General pathology studies common reactions of cells and tissues to injury or harmful stimuli.
• General pathology reactions are often not tissue-specific.
• An example of general pathology is a bacterial infection leading to acute inflammation in different tissues.
• Systemic pathology examines alterations and mechanisms in diseases of specific organ systems.
• Examples of systemic pathology include bone and soft tissue, gastrointestinal (GI), and genitourinary (GU) pathology.

Pathology in Medical Training and Board Certification

• Residency options include training in anatomic pathology (AP), clinical pathology (CP), or both.
• Anatomic pathology examines specimens removed during surgery or biopsy. It examines tissue architecture to diagnose diseases.
• Anatomic pathology aims to investigate and diagnose disease. It also aims to provide information for optimal clinical case management
• Clinical pathology involves laboratory analysis of body fluids and tissues.
• Clinical pathology's goals are investigation, diagnosis, and management decisions.
• A general pathologist is certified in both AP and CP.

Specialized Fields in Pathology

• Molecular pathology combines anatomic and clinical pathology with genetics, molecular biology, and biochemistry.
• Molecular pathology is used to study disease at the molecular level.
• Both AP and CP offer fellowship training options in subspecialties.

Surgical Pathology

• Surgical pathology examines surgical specimens to establish a diagnosis and guide clinical management.
• The workflow involves obtaining, examining, and diagnosing the specimen.
• Specimens originate from surgical procedures, biopsies, fine needle aspirates, or cell brushings.
• Non-biological specimens such as stents, orthopedic hardware, and bullet fragments are also examined.
• Surgeons, internal medicine specialists, radiologists, dermatologists, and OB/GYNs obtain specimens.
• OR nurses, couriers, pathology technicians, pathologist assistants, and histotechnologists are involved.
• Pathologists need to be familiar with the clinical aspects of the case (clinical-pathological correlation).
• Examination includes gross (macroscopic) and microscopic evaluations.
• Gross examination includes anatomical origin, size, weight, and description.
• Suspected anomalies are sectioned and stained (H&E) for microscopic examination.
• Additional tests used are immunohistochemistry, genetic sequencing, and electron microscopy.
• Frozen section examination provides intraoperative results to surgeons within 20 minutes.
• Findings guide immediate surgical management (e.g., tumor staging using TNM).
• TNM staging classifies tumors based on size, node involvement, and metastasis.
• Negative surgical margins indicate complete tumor removal.
• Positive margins indicate residual tumor requiring more excision.
• Combined AP/CP residency is 4 years (80% of residents); AP or CP only is 3 years.
• Fellowships generally last one year, with neuropathology lasting two.

Malignant Tumor TNM Staging System

• The TNM staging system classifies the extent and severity of malignant tumors.
• It guides treatment, predicts prognosis, and standardizes communication.
• T (Tumor) describes the size and extent of the primary tumor, from T0 (no tumor) to T4 (increasing size/invasion).
• N (Nodes) indicates spread to regional lymph nodes, ranging from N0 (no involvement) to N3 (increasing involvement).
• M (Metastasis) signifies distant spread, with M0 (no metastasis) and M1 (distant metastasis present).
• T3N1M0 means a large tumor invaded nearby structures with spread to a limited number of nearby lymph nodes and no distant metastases.
• TNM staging determines prognosis, guides treatment (surgery, chemotherapy, immunotherapy), and standardizes communication.

Cytopathology

• Focuses on free cells or cell clusters, unlike surgical pathology (tissues).
• Specimens are cells or cell clusters, rarely tissue fragments.
• Less invasive collection methods are used.
• Exfoliative cytology studies cells shed by the body or mechanically removed (e.g., Pap smears).
• Interventional cytology uses fine needle aspiration (FNA) to biopsy suspicious masses.
• Samples can be smeared on slides, stained, or centrifuged for examination.
• Examinations focus on cell morphology (shape, size, nucleus/cytoplasm ratio, abnormalities).
• "Adequacy" ensures samples are from the target area and diagnostic.
• Cytology detects pre-cancerous lesions, infections, immune diseases, and reactive changes.
• Cytopathology is applicable to nearly all organs and systems.
• The most common use is interpreting cells from the uterine cervix (Pap smear).
• Pap smears were developed by Dr. George Nicolas Papanicolaou in 1928.
• Aurel Babish first studied cervical cytopathology in 1927.
• Normal squamous epithelial cells exhibit maturation from basal to surface layers.
• Dysplastic cells are smaller with darker, irregular nuclei and abnormal nucleus-to-cytoplasm ratios.
• Carcinoma cells are pleomorphic, larger, and darker, with inflammation and signs of hemorrhaging.

Forensic Pathology

• Examines corpses, remains, or lesions related to crimes.
• It is an application of medical jurisprudence, varying by country and state.
• First recognized by the American Board of Pathology in 1959, and in Canada in 2003.
• Autopsy is a standardized examination of a corpse to answer medical and legal questions.
• Clinical autopsy investigates natural deaths (hospital), aiming to diagnose, confirm findings, or evaluate treatment.
• Forensic autopsy investigates deaths with no obvious natural cause, or with suspicious circumstances (accidents, suicides, homicides).
• Forensic autopsies establish identity, context (time, place, manner of death), and collect legal evidence.
• Manner of death encompasses mode, physiopathology, cause, and mechanism.
• An interdisciplinary effort is used, including physiology, pathology, toxicology, physics (ballistics), geology (soil analysis), and entomology (time of death).
• Authorized by a judicial entity (court, coroner, medical examiner).
• Homicides are less common than suicides and accidents.
• Dr. Miklos Nissly was an Auschwitz prisoner forced to perform autopsies on victims.
• COVID-19 autopsies were both clinical (research) and forensic (public threat).
• Microscopic lung images show infected (red) vs. normal (blue) cells.
• Post-mortem degradation of the virus was noted.