Week 12 Selected Cancers Fall 24 Student PDF

PATH 1017: Selected Cancers Professor Jennifer Lamarre PATH 1017 2024-2025 1  Canadian Statistics: Types of Cancer Lung, prostate, breast and colorectal cancer account for 50% of all new cancer cases every year. – Breast Cancer: 28% of new cancer cases in women. –...

PATH 1017: Selected Cancers Professor Jennifer Lamarre PATH 1017 2024-2025 1  Canadian Statistics: Types of Cancer Lung, prostate, breast and colorectal cancer account for 50% of all new cancer cases every year. – Breast Cancer: 28% of new cancer cases in women. – Prostate Cancer 27% of new cancer cases in men. Leading cause of premature death – 1 out of every 4 Canadians will die from cancer Age over 70 years accounts for 60% of all cancers deaths Lung Cancer: 27% of all cancer deaths each year. 5 year survival rate: 60% PATH 1017 2024-2025 2 Cancers in Young Adults (15- Different patterns 25y) – Lymphomas (Hodgkin & Non-Hodgkin) most common cancer – Thyroid (M & F) – Testicular (M); – Melanoma (M & F) 10,000 new diagnoses each year – 2/3 in young women Main cause of premature death in young women – Mortality decreasing, but 2,000 will die Key prevention: – Smoking cessation; avoiding sun exposure; Pap test; HPV vaccination PATH 1017 2024-2025 3  Cancers in Children (0-15y) Little known about childhood cancers – Theories: genetics, environmental, radiation/drug exposures Leading cause of non-injury related death – 850 children diagnosed each year – 135 deaths each year (declining) – 82% survival rate Males 1.2X > females Highest incidence: 0-4 years PATH 1017 2024-2025 4  Cancer in Children (0-15y) Most common types of childhood Why are cancers: childhood – Leukemia cancers often – CNS cancers overlooked? – Lymphomas Childhood Tumours: – shorter latency period – rapid growth – more aggressive & invasive, – frequently spread elsewhere in body PATH 1017 2024-2025 5  Cancer in Childhood Warning signs: Are there effects of cancer treatment – Prolonged fever that present later – Unexplained weight loss in life? – Growing masses Diagnostic tests &treatment similar to those used in adult cancers – Doses of chemotherapy, radiation etc. have to adjusted – Long-term follow-up needed for late effects in survivors PATH 1017 2024-2025 6 LUNG CANCER PATH 1017 2024-2025 7  Lung Cancer Second leading cancer 5 year survival rate: – 13% (M); – 17% (F) Risk Factors – Smoking – Occupational exposures PATH 1017 2024-2025 8  Lung Cancer Arises from epithelial cells lining the lungs Aggressive, invasive & metastasize 4 sub-types – Small-cell lung cancer – Non–small-cell lung cancer º Large-cell carcinoma º Squamous cell All types can cause º Adenocarcinoma paraneoplastic syndromes PATH 1017 2024-2025 9  Lung Cancer Highly Small cell lung cancer (25-40%)capable of producing – Distinct cell type affected bioactive Small, round oval cells growing in clusterssubstances – Strong link to cigarette smoking – Highly malignant and spreads at early stages – Metastasis often present at diagnosis – Treatment: Surgery not offered Treated with chemotherapy +/- radiation 50% die within 12-15weeks PATH 1017 2024-2025 10  Lung Cancer Non-Small Cell Lung Cancers: Squamous cell carcinoma: – Mostly in male smokers – Associated with smoking – Arises in central bronchi within the lumen and spreads centrally in lung – May be detected though sputum cytology – More amendable to treatment PATH 1017 2024-2025 11  Lung Cancer Non-Small Cell Lung Cancers Adenocarcinoma (25-40%): – Most common lung cancer in women & non-smokers – Arise in bronchioles or alveoli and are located more peripherally in lung – Associated with scarring of lung from other conditions (i.e.. TB) – Poorer prognosis PATH 1017 2024-2025 12  Lung Cancer Non-Small Cell Lung Cancers Large Cell Carcinomas – Large polygonal cells Difficult determine underlying cell type (anaplasia) – Arise in periphery of lung then invade bronchi and larger airways – Metastasis occur early – Poor prognosis PATH 1017 2024-2025 13 Lung Cancer Manifestations Often very subtle onset until advanced May mimic other respiratory illnesses Manifestations vary according to: – Location of tumour in lung – Presence of local spread and metastasis – Development of paraneoplastic syndromes PATH 1017 2024-2025 14 Lung Cancer Manifestations Earliest: chronic cough, Why would SOB, wheezing lung cancers Hemoptysis cause these Pain manifestation Hoarseness s? Dysphagia Other: fatigue; weight loss PATH 1017 2024-2025 15  Lung Cancer Complications Superior vena cava What syndrome manifestation – Uncommon s would be observed? – Tumour or lymph nodes compress SVC & interrupt blood flow – Interferes with blood drainage from head, neck, chest PATH 1017 2024-2025 16  Lung Cancer Complications Pleural effusion What – Collection of fluid manifestation develops when pleural s would be layers involved observed? – Can lead to lung compression, dyspnea PATH 1017 2024-2025 17  Lung Cancer Complications Paraneoplastic Hypercalcemia Cushing syndromes: (parathyroid syndrome hormone) (ACTH)  small squamous cell Tumours able CA cell CA to synthesize SIADH- bioactive Syndrome of products Inappropriate Anti-diuretic Hormone  May occurs small cell CA with Hematologic Neuromuscular bronchogenic disorders  syndromes  adenocarcinoma neoplasms s small cell CA PATH 1017 2024-2025 18 Lung Cancer Complications Metastasis spread – Lymph and vascular system spread cancer – Found in 50% pts at diagnosis – 90% develop at some point – Target sites? PATH 1017 2024-2025 19  Diagnostics: Lung cancer Diagnosis: – History & physical – CXR – Bronchoscopy – Sputum cytology – Percutaneous lung tissue biopsy – Additional tests: CT, MRI, ultrasound to better identify and stage tumour and to identify metastasis PATH 1017 2024-2025 20  Treatment- Lung cancer Treatment: – Small cell CA- – Chemotherapy, radiation therapy – Non-small cell CA- – Surgery – Radiation therapy – Chemotherapy Palliation if advanced Prognosis: very poor PATH 1017 2024-2025 21 COLORECTAL CANCER PATH 1017 2024-2025 22  Adenomatous polyps - Adenomas Benign neoplasms arising from epithelial mucosal ling of intestines – Classified and named according to area of growth: Tubular, Villous , Tubulovillous Overgrowth of tissue (neoplasia) occurring due to abnormalities in crypt cells leading to accumulation of mucosal cells called polyps Why are these often removed? PATH 1017 2024-2025 23  Colorectal Cancer- Adenocarcinoma Why is diet a Risk Factors: risk factor in – Age>50y the – Family history development of – GI conditions (i.e. Ulcerative colorectal colitis) cancer? – Polyps – Diet What are some of the protective 1/3 who develop colorectal factors? adenocarcinoma will die PATH 1017 2024-2025 24 Manifestations of colorectal cancer What are some of the manifestations of colorectal cancer? What is the main symptom that causes a person to seek medical attention? PATH 1017 2024-2025 25  Diagnostics: colorectal cancer Diagnosis: History & physical (DRE) Tests: – Occult blood stool test – Sigmoidoscopy or colonoscopy – Barium x-ray – Histology of tumour specimen – Blood for tumour markers – which one? – Other tests to assess for spread- CT etc. PATH 1017 2024-2025 26 Colorectal Cancer Screening Cancer Care Ontario recommends… starting at age 50: – Annual occult blood stool test – Sigmoidoscopy or barium enema Q5y If high risk, screening begins earlier PATH 1017 2024-2025 27  Treatment - Colon Cancer Treatment – Surgical removal: colectomy; colon resection; colostomy Sometimes pre-surgery radiation Post-op chemotherapy – Chemotherapy and radiation may be used for palliative treatment Prognosis depends on: – stage – amount of bowel involved – metastasis present at diagnosis PATH 1017 2024-2025 28 TESTICULAR CANCER PATH 1017 2024-2025 29  Testicular Cancer Most common cancer in males 15-35y 5 year survival rate: >95% Highly curable Etiology: unknown Predisposing factors: Cryptorchidism- undescended testes Genetics Disorders of testicular development Most common in Caucasians PATH 1017 2024-2025 30  Testicular Cancers Usually arise from germ cells – Capable of: Differentiating into different cell types Secreting hormones including those from earlier stages of development May be classified as seminomas and non- seminomas based on cell type and differentiation – Seminomas- uniform cell type – Non-seminomas- more than one cell type, less differentiated PATH 1017 2024-2025 31  Manifestations - Testicular Cancer Manifestations: – First sign- Slight enlargement of testicle with some degree of discomfort – Others: Ache in groin or abdomen Scrotal heaviness Gynecomastia What is the pathophysiolog – Late stages- More severe pain y of gynecomastia? PATH 1017 2024-2025 32  Diagnostics: Testicular Cancer Diagnosis : – Early detection – History & Physical – Tests: Ultrasound CT/MRI Blood- tumour markers: What are – tumor – markers ? – Histology of tumour specimen PATH 1017 2024-2025 33 Treatment: Testicular Cancer Treatment: – Orchiectomy – Chemotherapy – Radiation therapy – Ongoing follow-up Prognosis: good if early tx Metastasis are possible PATH 1017 2024-2025 34 PROSTATE CANCER PATH 1017 2024-2025 35 Benign Prostatic Hyperplasia Age-related, Manifestations nonmalignant – Trouble starting enlargement of the urination prostate gland – Nocturia Characterized by the – Urinary retention formation of large, discrete lesions in the periurethral region of the prostate rather than the peripheral zones, which commonly are affected by prostate cancer PATH 1017 2024-2025 36  Prostate Cancer Unknown cause for prostate Cancer Risk factors: – age – Race – Heredity – Hormone levels – Environmental influences Most common is prostatic adenocarcinoma PATH 1017 2024-2025 37  Manifestations Asymptomatic in Screening early stage – DRE Symptoms often – PSA testing suggest metastatic – Transrectal spread ultrasonography – urgency – Frequency – Nocturia – Blood in ejaculate DRE – nodular and fixed prostate PATH 1017 2024-2025 38  Diagnosis and Treatment of Prostate Cancer Biopsy Watchful waiting Surgery Gleason Radiation therapy score High-intensity Tumor focused ultrasound markers Chemotherapy Cryosurgery Hormonal therapy Combination PATH 1017 2024-2025 39  Methods of Staging Tumors CT scans of the chest, abdomen, and pelvis Ultrasonography for detection of bulky inferior nodal metastases Lymphangiography Radiographic methods to detect metastatic spread PATH 1017 2024-2025 40  Prostate Tumor Grading System T1: Primary-stage tumors are asymptomatic and discovered on histologic examination of prostatic tissue specimens. T2: Tumors are palpable on digital examination but are confined to the prostate gland. T3: Tumors have extended beyond the prostate. T4: Tumors have pushed beyond the PATH 1017 2024-2025 41  Treatment Surgery – Radical prostatectomy Radiation therapy Hormonal manipulation – Androgen deprivation therapy for metastatic disease PATH 1017 2024-2025 42  Factors Protective Against Prostate Cancer Dietary factors such as lycopene, selenium, and vitamin E Chemoprevention (using drugs to prevent disease) with the 5α-reductase inhibitor Finasteride was recently shown to prevent the development of prostate cancer in men without BPH. PATH 1017 2024-2025 43 ENDOMETRIAL (UTERINE) CANCER PATH 1017 2024-2025 44  Leiomyomas (Fibroids) Benign neoplasms of smooth muscle in uterus – Also called myomas and fibroids – occur in 1:5 women over 35 years Develop within layers of uterus: – Submucosal, Subserosal, Intramural Growth in response to estrogen – Increase in size during pregnancy or with estrogen stimulation (i.e.. HRT) – What effect does menopause have? PATH 1017 2024-2025 45  Leiomyomas (Fibroids) Often discovered on routine pelvic exam Confirmed with ultrasound Manifestations: – Often asymptomatic – Menorrhagia – Anemia – Urinary frequency – Rectal pressure/ constipation – Abdominal distension – Pain (uncommon) Treatment – if causing problems- myomectomy, hysterectomy PATH 1017 2024-2025 46  Endometrial Cancer- Adenocarcinomas Most common invasive cancer of female reproductive tract –7% of all invasive cancers in women Primarily affects Post-menopausal women 55-65y 15-25% of post-menopausal women with bleeding have endometrial cancer Uncommon in women under 40y PATH 1017 2024-2025 47  Types of endometrial cancer- adenocarcinoma Type I – 80% of the cases – Arise in women with estrogen excess – Well differentiated Type II – Arise in women with endometrial atrophy and who do not have excess estrogen – Usually age-related mutations – Poorer prognosis PATH 1017 2024-2025 48 Risk Factors for endometrial cancer Prolonged estrogen stimulation with hyperplasia of endometrium Conditions that alter estrogen levels: – Obesity – Anovulatory menstrual cycles – Estrogen secreting neoplasms – Unopposed estrogen therapy Age-related PATH 1017 2024-2025 49  Endometrial Cancer Manifestations: Diagnostic tests: – Abnormal, painless – Trans-vaginal bleeding ultrasound – Endometrial biopsy Late- (D&C procedure- – cramping, pelvic dilatation and pain, curettage) – lower abdominal In post-menopausal discomfort, women, any bleeding is – Post-coital bleeding considered – Enlarged lymph abnormal and needs investigation nodes PATH 1017 2024-2025 50  Treatment - Endometrial Cancer Treatment: – Surgery – Radiation Prognosis- – 5 year survival is 90% with early diagnosis and treatment PATH 1017 2024-2025 51 BREAST CANCER PATH 1017 2024-2025 52  Breast Cancer Leading cause of CA in women Higher rates due to better detection 5-year survival rate: 87% –Mortality has decreased but is still the second leading cause of cancer deaths in women PATH 1017 2024-2025 53  Breast Cancer Risk Factors: – Gender Most – Age women – Family history of breast CA (5-10%) with Breast CA have no – Prior breast cancer identifiable – History of benign breast disease risk factors – Hormonal influences – Early menarche – Late menopause – Pregnancies- first birth after 30y; no term births PATH 1017 2024-2025 54  Breast Cancer – BRCA 1 &2 Cancer develops when cells mutate & are not repaired – BRCA1 and BRCA2 genes code for proteins that help repair DNA after it has mutated (tumour suppressor genes) – Mutation of BRCA1 or BRCA2 makes breast and ovarian cancer more likely – Responsible for 80% of cancers in women under 50y PATH 1017 2024-2025 55  Breast Cancer- Hormone Receptor Role Estrogen also has a role in breast cancer Estrogen and other growth factors make breast cells divide Breast cells with too many estrogen or growth factor receptors are more likely to become cancerous HER1, HER1-2 Helpful in treatment and improves prognosis PATH 1017 2024-2025 56  Breast Cancer There are different Ductal carcinoma in situ types of breast Invasive carcinoma cancer. – Invasive ductal carcinoma They are diagnosed Triple negative by their locations, invasiveness, and hormone receptor presence (or absence) PATH 1017 2024-2025 57  Breast Cancer manifestations Mass on palpation: – Solitary mass – Painless – Firm, fixed – Poorly defined borders Puckering Nipple retraction Unusual discharge Change in shape PATH 1017 2024-2025 58  Breast Cancer Screening Cancer Care Ontario Screening Guidelines: Age Recommendation 50-74 Mammogram at least Q2Y 74 + Screening dependant on assessment of risk If high Start screening at 30y- mammogram risk and breast MRI annually PATH 1017 2024-2025 59  Diagnostics: Breast Cancer Physical exam Mammogram Ultrasound Needle aspiration or excisional biopsy (lumpectomy) Specimens for: – Cytology & histology studies – Hormone receptor status Others: – CT, MRI if BRCA+ – Also investigate for spread – Lymph node biopsy PATH 1017 2024-2025 60  Treatment: Breast Cancer Treatment: – Surgery – Radiation – Chemotherapy – Hormonal manipulation Prognosis predicted by lymph node involvement PATH 1017 2024-2025 61  Breast Cancer Hormonal Therapy: Ex.-Tamoxifen – Nonsteroidal anti-estrogen drug – Binds to estrogen receptors and blocks estrogen effect on the growth of malignant cells – Improves survival, decrease recurrence and decrease mortality PATH 1017 2024-2025 62 NEVI & SKIN CANCERS PATH 1017 2024-2025 63  Nevi Nevi are benign congenital or acquired tumors of the skin. Melanocytic nevi are pigmented skin lesion from proliferation of melanocytes in epidermis or dermis. – Tan to deep brown, uniformly pigmented, small papules with well-defined rounded borders. PATH 1017 2024-2025 64  Nevi and skin cancers Junctional nevi are oval melanin-containing cells that grow into nests or clusters along dermal-epidermal junction. Compound nevi contain epidermal and dermal components. Dysplastic nevus can transform into malignant melanoma. – Usually larger than other nevi (>5 mm), flat, slightly raised plaque with a pebbly surface PATH 1017 2024-2025 65  Nevi and skin cancers Vast majority of dysplastic nevi are stable and never progress, vest viewed as markers for melanoma risk. Due to possibility of melanoma, any mole that undergoes a change required immediate medical attention. – Change is size, thickness or colour, itching, bleeding. PATH 1017 2024-2025 66  Malignant melanoma Malignant tumor of the melanocytes. Rapid increase over past few decades due to increased UV exposure. Risk factors include; – family history – fair hair and skin – tendency to freckle – history of sunburns as a child – atypical moles/dysplastic nevus syndrome PATH 1017 2024-2025 67  Malignant melanomas Differ in size and shape. Slightly raised and black or brown, borders irregular and surfaces uneven. Arise from preexisting nevi or new molelike growths. Dark melanomas mottled with shades of red, blue and white. Melanoma growth (blue), inflammation (red), scar formation (white) PATH 1017 2024-2025 68  4 Types of Melanomas Classification is based on radial & vertical growth 1. Superficial spreading- 70% Raised edges; grow horizontally and vertically Ulcerate and bleed 2. Nodular- 15%–30% Dome-shaped, blue-black 3. Lentigo maligna -4%–10% Slow growing, flat 4. Acral lentiginous -2%–4% On palms, soles, nail beds, mucous membranes PATH 1017 2024-2025 69  Early detection Regular self-exam of total skin surface. ABCD rule for early diagnosis and treatment; Asymmetry Border irregularity Colour variation Diameter (greater than ¼ inch) Evolving – dynamic nature of PATH 1017 2024-2025 70 melanomas  Diagnosis and treatment Diagnosis based on biopsy findings from lesion. Staged using TNM (tumor, lymph node and metastasis staging system) from 0-4. Treatment is usually surgical excision. – No effective chemotherapy. – Controversial interferon therapy. PATH 1017 2024-2025 71  Basal cell carcinoma Carcinoma of the nonkeratinizing cells of the basal layer of the epidermis. Most common invasive cancer in humans. Occur in fair-skinned persons with history of long- term sun-exposure. Slow-growing tumors that extend wide and deep if left untreated, but rarely metastasize. PATH 1017 2024-2025 72  Basal cell carcinoma Risk factors for spread include: – tumor diameter of greater than 2 cm – location on central part of face or ear – long standing duration – incomplete excision and perineural or perivascular involvement. Two types of basal cell carcinoma; – Nodular basal cell carcinoma – Superficial basal cell carcinoma PATH 1017 2024-2025 73  Basal cell carcinoma Highly curable if detected early. All suspected lesions should undergo biopsy. Treatment goal is complete elimination of the lesion. PATH 1017 2024-2025 74  Squamous cell carcinoma Second most common malignant tumors from sun-exposed sites in older people. Risk factors; – increased UV exposure – strong occupational hazard (industrial tars, coal) – men more prone. Two types; – Intraepidermal squamous cell – Invasive squamous cell PATH 1017 2024-2025 75  Squamous cell carcinoma Red-scaling, keratotic, slightly elevated lesion with an irregular border, with a shallow chronic ulcer. With time, lesions grow outward, show large ulcerations, have persistent crusts and raised reddened borders. Occur on sun-exposed areas; nose, forehead helix of the ear lower lip back of the hand. PATH 1017 2024-2025 76