BGDA - Pathology and Infertility

Neoplasm

disorder of growth triggered by acquired (or sometimes inherited) mutations affecting a single cell and its clonal progeny.

Benign neoplasms

tumours that remain localised and do not invade or metastasise. May still cause disease depending on size, site, and functional activity.

Malignant neoplasms (cancers)

invade and destroy adjacent structures and spread to distant sites.

Carcinoma

cancers from epithelial origins.

Sarcoma

cancers from mesenchymal origins, i.e. body's connective and supportive tissues e.g. from bone, muscle, fat.

Leukemia

cancers from blood-forming tissues (haematapoetic), including the bone marrow and the lymphatic system

Lymphoma

cancers from lymphatic system, i.e. white blood cells.

Metaplasia

replacement of one mature, specialised cell type with another mature cell type that is better suited to handle chronic stress or irritation.

Differentiation

degree to which the tumour resembles normal tissue, i.e. a well-differentiated tissue will closely resemble normal tissue.

Anaplasia

lack of differentiation and abnormal cells, associated with malignant tumours.

Pleomorphism

variation in cell size and shape, a type of cytological atypia seen in many malignant cancers.

Increased N:C ratio, nuclear pleomorphism, hyperchromasia, coarse chromatin, prominent nucleoli

List 5 characteristics of abnormal nuclear morphology.

Increased N:C ratio

abnormal nuclear morphology, enlarged nuclei relative to cytoplasm.

Nuclear pleomorphism

abnormal nuclear morphology, variable nuclear size and shape.

Hyperchromasia

abnormal nuclear morphology, darkly staining nuclei.

Coarse chromatin

abnormal nuclear morphology, irregular, clumped chromatin distribution.

Prominent nucleoli

abnormal nuclear morphology, large or multiple nucleoli.

Abnormal nucleus, atypical mitosis, tumour giant cells, loss of polarity, multi-nucleated cells

List 5 examples of pleomorphism associated with cancer.

Atypical mitosis

pleomorphism indicating cancer, increase in mitotic figures, displaying abnormal shapes.

Tumour giant cells

pleomorphism indicating cancer, considerable larger than neighbouring cells, often possess a large nucleus or several nuclei.

Loss of polarity

pleomorphism indicating cancer, cells grow in sheets with loss of normal orientation and absence of identifiable growth patterns.

Dysplasia

disorderly growth in epithelial cells characterised by cytological atypia and architectural disorganisation that MAY lead to malignant transformation.

Cytological atypia

cells that appear abnormal under a microscope.

Carcinoma in situ

severe dysplasia involving the full thickness of the epithelium but does NOT penetrate the basement membrane.

Benign growth

grow as a cohesive, expansile mass, remaining localised to site of origin, often developing with a capsule due to slow expansion.

Malignant growth

growth is accompanied by progressive invasion and destruction, disrupting surrounding tissue architecture.

Local invasion

malignant tumours growing past normal anatomic boundaries.

Poorly demarcated margins

common feature of malignant growth, makes surgical resection difficult, large margin must be excised of apparently normal tissue.

Metastasis

spread of primary tumour to physically discontinuous sites, forming secondary tumours, unequivocally marking the tumour as malignant, through blood vessels, lymphatics, or body cavities.

Proto-oncogenes

usually promote cell growth, division, or survival, become oncogenes when overactivated, causing uncontrolled cell proliferation.

Tumour suppressor genes

genes that regulate cell division and appearance of abnormal cells, their inactivation allows cancer cells to develop.

DNA repair genes

genes that repair DNA damage, mutation causing genomic instability results in accumulation of errors, raising the risk of cancer.

Apoptosis regulating genes

genes that control apoptosis, when disrupted allow abnormal cells to avoid death, promoting tumour formation.

Tumour heterogeneity

tumour with multiple genetically diverse lineages as new mutation confer selective growth advantages.

Cancer cachexia

primarily a feature of malignant neoplasms, hypercatabolic state defined by a loss of muscle mass that cannot be explained by diminished food intake.

Paraneoplastic syndromes

symptoms of cancer not related to tumour location or normal hormone production, most commonly associated with malignant neoplasms.

Chronic inflammation

prolonged response from persistent stimuli where simultaneous inflammation and repair occur.

Macrophages, lymphocytes, plasma cells, fibroblasts

What are the 4 main cells involved in chronic inflammation.

Persistent infection, autoimmune disease, prolonged irritant exposure

Name 3 common causes of chronic inflammation.

Cytokines, growth factors, macrophage enzymes

List 3 typical mediators of chronic inflammation.

Acute on chronic

sudden, severe flare-up of a long-standing, ongoing illness.

Acute onset

chronic inflammation progresses from acute inflammation when stimulus is not cleared, e.g. upper respiratory infection.

Chronic onset

chronic inflammation has insidious onset, gradually developing symptoms, e.g. atherosclerosis, rheumatoid arthritis.

Monocytes/Macrophages

leucocytes that phagocytose pathogens and debris, present antigens to the adaptive immune system and release cytokines and growth factors that regulate inflammation and tissue repair.

Lymphocytes

immune cells (T and B cells) that mediate adaptive immune responses by recognising specific antigens and coordinating immune activity

Hypothalamic changes, acute phase proteins

What are the 2 means by which cytokines cause systemic effects in chronic inflammation?

Cardinal signs, marked vascular response

What are 2 features less prominent in chronic inflammation compared with acute?

C-reactive protein

binds to microbes and damaged cells as an opsonin, enhancing phagocytosis and activating complement → key blood marker of inflammation.

Fibrinogen

clotting protein converted to fibrin during coagulation, increasing the erythrocyte sedimentation rate (ESR).

Serum Amyloid A Protein (SAAP)

helps recruit immune cells among other roles, BUT persistent elevation can lead to AA amyloidosis; deposition of amyloid protein in organs = dysfunction.

Hepcidin

regulates iron metabolism, blocking iron absorption from the gut, reducing iron availability causing anaemia of chronic disease.

Thrombopoietin

stimulates platelet production in bone marrow, causing reactive thrombocytosis (increased platelet count) during chronic inflammation.

Granulomatous inflammation

morphological pattern of chronic inflammation induced by an agent resistant to eradication resulting in a discrete collection of activated macrophages.

Epithelioid macrophages

activated macrophages with abundant pink cytoplasm clustered close together; defining cell of the granuloma.

Multinucleated giant cells

formed by the fusion of macrophages.

Lymphocyte rim

surrounded by T-cells that help maintain the granulomatous response.

Fibrosis

fibrous capsule commonly developed in older, chronic granulomas due to fibroblast activation.

Caseation

central necrosis present with certain infections (Tuberculosis) due to hypoxia and reactive species released by damaged macrophages.

Epithelioid macrophages, multinucleated giant cells, lymphocyte rim, fibrosis, caseation

List 5 common features of granulomatous inflammation.

Caseating granuloma

granuloma classically associated with TB and some fungal infections, with central necrosis, giant cells, and lymphocyte rim.

Non-caseating granuloma

granuloma with no central necrosis, common in Sarcoidosis and Crohn’s disease, or with foreign-bodies, with well-formed epithelioid macrophage aggregates.

Asthma

recurrent acute on chronic inflammation of the airways, brought on by various stimuli, characterised by eosinophil-rich inflammation.

Peptic ulcer disease

chronic mucosal ulceration in the stomach or duodenum causing bleeding and acid entering abdominal cavity, commonly due to drug or bacteria-induced damage.

Rheumatoid arthritis

chronic autoimmune disease with immune destruction of joints, causing synovial hyperplasia and eventual cartilage and bone erosion.

Ulcerative colitis

chronic inflammatory bowel disease with inflammation and ulcers in the lining of the large intestine, with distortion and loss of crypts.

Crohn’s disease

chronic inflammatory bowel disease that causes long-term inflammation in the digestive tract, characterised by non-caseating granulomas.

Chronic kidney disease

progressive and irreversible loss of kidney function due to long-standing damage, characterised by tubal atrophy.

Tuberculosis

chronic infectious disease caused by Mycobacterium tuberculosis, characterised by granulomatous inflammation with caseous necrosis.

Vaginal discharge

common clinical presentation associated with infection or inflammation of the genital tract.

Vaginal bleeding in pregnancy

common clinical presentation with placental causes (previa, abruption, miscarriage) or ectopic pregnancies.

Post-coital vaginal bleeding

common clinical presentation associated with cervical cancer.

Post-menopausal vaginal bleeding

common clinical presentation associated with carcinoma polyps or endometrial carcinoma.

Pelvic/abdominal pain

common clinical presentation associated with distension/rupture, ovarian torsion, menstrual pain due to endometriosis.

Abdominal distension

common clinical presentation associated with ascites, uterine enlargement, ovarian cysts.

Abnormal menstruation

common clinical presentation associated with hormonal imbalances, structural issues in the uterus (like fibroids or polyps), or bleeding disorders.

Polymenorrhea

menstrual cycles occurring at < 21 day intervals → usually benign; maybe hormonal dysfunction.

Oligomenorrhoea

menstrual cycles occurring at intervals > 35 days → maybe PCOS, endocrine disorders, or hypothalamic dysfunction.

Metrorrhagia

irregular intermenstrual bleeding → clinically important; maybe cervical or endometrial pathology.

Hypermenorrhea

excessively heavy menstrual flow with normal cycle duration → can lead to iron deficiency anaemia.

Menorrhea

menstrual bleeding lasting > 7 days → maybe pathology or coagulation disorders.

Menorrhagia

excessive menstrual blood loss occurring at regular intervals → clinically important; common cause of anaemia and may indicate fibroids, adenomyosis, malignancy.

Menometorrhagia

heavy, prolonged, and irregular bleeding with intermittent spotting → potentially serious; maybe malignancy, pregnancy complications, or endocrine disease.

Dysmenorrhea

painful menstruation → usually benign; maybe endometriosis or adenomyosis if severe.

Ascites

an abnormal buildup of excess fluid in the peritoneal cavity.

Precocious puberty

puberty occurring too early, under the age of 8 in girls.

Anovulatory cycle

a menstrual cycle where the ovaries fail to release an egg, leading to abnormal hormone levels and uterine cycle phases.

Pelvic inflammatory disease (PID)

ascending infection spreading to cervix, uterus, uterine tubes, ovaries, and peritoneal cavity, mainly caused by STIs, postpartum infections, and genitourinary tract TB.

Abdominal/pelvic pain, dyspareunia followed by spotting, abnormal vaginal discharge, fever and chills

List clinical manifestations of PIDs.

Neisseria gonorrhoeae

non-capsulated, gram-negative diplococcus pathogen causing Gonorrhoea.

Abundant pus

neiserria gonorrhoeae adheres to mucosa, invades and trigger a strong neutrophilic response, leading to what?

Acute urethritis

inflammation of the urethra, often characterized by a sudden onset of burning pain during urination (dysuria), itching, and sometimes a cloudy or purulent discharge, common with STIs in men, making them treated sooner.

Disseminated gonococcal infection

rare complication of Neisseria gonorrhoeae infection one in blood stream. Causing rashes, septic arthritis, endocarditis, and meningitis.

Chlamydia trachomatis

gram-negative obligate intracellular bacterium, where they proliferate in mucosal epithelium as reticulate bodies.

Elementary bodies

form by which chlamydia trachomatis is transmitted between cells.

Lymphogranuloma venereum (LGV)

infection caused by highly invasive strain that enters the lymphatic system characterised by punched-out lesions, but also forming granulomas, fibrosis, fistulas, and lymphatic obstruction.

Ectopic pregnancy

implantation of zygote outside the uterine cavity, commonly the uterine tube.

Amenorrhoea

absence of periods, or slight spotting during expected menses.

Pain, amenorrhoea, abnormal bleeding, pregnancy symptoms

List 4 classic clinical manifestations of ectopic pregnancy.

Positive beta-HCG test, transvaginal ultrasound

What are the typical tests done to diagnose ectopic pregnancies?

Endometrial biopsy

If the location of the embryo cannot be confirmed by ultrasound, what other diagnostic test can be performed to confirm an intrauterine pregnancy has NOT occurred (no chorionic villi tissue present).