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Oncology (solid tumors) by Mind Map: Oncology (solid tumors)
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Oncology (solid tumors)

Thoracic Malignancies

Thymic Neoplasms

Epidemiology 1. Thymic neoplasms, mostly thymomas, constitute 30% of anterior mediastinal masses in adults 2. Thymic carcinoma is much less common

Clinical Presentation 1. Nearly one-half are asymptomatic and are discovered on routine radiographs 2. In symptomatic patients, 40% of patients with thymoma have myasthenia gravis 3. 70% of patients with thymoma have some form of a paraneoplastic syndrome including lupus, polymyositis, myocarditis, Sjogrens, ulcerative colitis, Hashimotos thyroiditis, Rheumatoid Arthritis (RA), sarcoidosis, scleroderma, endocrine disorders, blood disorders such as pure red cell aplasia, hypogammaglobulinemia 4. Others complain of chest pain or dyspnea 5. May metastasize to pleural, lung, bone

Work-up 1. CT chest is primary modality for staging 2. Octreotide scans may be helpful for staging and determining potential response to octreotide

Pathology 1. 90% of thymomas occur in the anterior mediastinum 2. Most are lymphocyte predominant and may be confused with lymphomas 3. Thymic carcinomas are a distinct entity, less common, and more aggressive

Treatment 1. The primary treatment for thymic neoplasms is surgery 2. Chemotherapy and radiation are used to treat more advanced disease 3. Steroids can reduce tumor size but it only really treats the inflammatory component of the cancer and not the malignant cells 4. Octreotide may have a role in some patients

Lung Cancer

Epidemiology 1. Leading cause of cancer-related death in both men and women 2. Tobacco accounts for approximately 90% of all cases 3. Other risks for lung cancer include: second hand smoke, radon, asbestos, heavy metals, ionizing radiation; cooking fumes (Asia), chronic injury/inflammation

Clinical Presentation 1. Local chest symptoms: cough, hemoptysis, dyspnea, hoarseness (recurrent laryngeal nerve compression by tumor or mediastinal lymphadenopathy), SVC syndrome resulting in facial/neck/arm swelling; malignant pleural effusions are common due to tumor infiltration of pleura causing mechanical breaks in microvasculature lining pleura 2. Systemic symptoms: bone pain, weight loss, cachexia, fatigue 3. Paraneoplastic syndromes (more common in small cell lung cancer) such as SIADH (hyponatremia), Cushings syndrome (due to secretion of ACTH), Eaton-Lambert syndrome (anti-calcium channel antibodies), cerebellar degeneration (anti-HU antibodies); hypercalcemia (due to bone mets or secretion of PTH-RP) is more common in squamous cell cancer; mid-tibia pain or clubbing is usually indicative of hypertrophic osteoarthropathy (HPO) 4. Lymphatic spread usually peribronchial, hilar, then mediastinal and upper tumors to the neck (supraclavicular, scalene) 5. Hematogenous spread to the bone, brain, liver, adrenals most commonly

Work-up 1. Sputum cytology for patients with a productive cough, hemoptysis, or central, cavitating tumors may yield a diagnosis (usually squamous cell type) 2. CT chest and abdomen 3. Brain imaging (CT or MRI), bone scan (if PET not done) 4. PET scan standard for most patients with potentially resectable NSCLC 5. Evaluation of the mediastinum is essential for NSCLC and may be achieved by CT, PET, endoscopic ultrasound of the esophagus (EUS), endoscopic endobronchial ultrasound (EBUS), or mediastinoscopy 6. Bronchoscopy for biopsy if central lesion, CT-guided biopsy if peripheral 7. Evaluation for fitness for surgery, if surgically resectable disease for NSCLC, primarily with cardiopulmonary testing, including FEV-1 (usually requires a post-op predicted FEV-1 of approximately 0.8 or 40% predicted; pre-op requirements are around FEV-1 > 1.2 or 60% predicted for lobectomy and FEV-1 >1.6 or 80% predicted for pneumonectomy)

Pathology, 1. Small Cell (central location, aggressive, early hematogenous spread with high propensity for brain mets; highly smoking related); stain positively for neuroendocrine markers such as chromogranin and synaptophysin; high mitotic rate; TTF-1 positive; extensive necrosis in pathology specimen, 2. Non- Small Cell: Squamous cell (highly smoking related, central lesions, cavitary in many cases); usually stain positively for p63. Adenocarcinoma (usually smoking related, but NOT ALWAYS, peripheral lesions; most common subtype); usually stain positively for TTG-1; 25% harbor K-ras mutations (almost exclusive to smokers); some smokers may have ALK gene re-arrangements, although this is much more commonly seen in non-smokers; EGFT mutations are seen in 50% of non-smokers w/ adenocarcinoma. Large cells (highly smoking related, agressive subtype)

Treatment 1. Non-small cell lung cancer: stage I (lung only)-II (lung + hilar LN) surgery is the standard; cures in about 2/3 stage I patients and 45% stage II patients; stage III chemo/radiation with cure rate of about 20%; stage IV palliative chemotherapy; molecularly targeted therapy for select patients (EGFR mutations or ALK gene rearrangements or ROS-1 rearrangements) 2. Small cell lung cancer: limited stage disease—chemo/radiation (20% cure); metastatic disease---chemotherapy only (median survival time 8-10 months) 3. Performance status is the most important prognostic variable when estimating chances of benefiting from treatment for patients with metastatic disease

Thyroid Cancer

Epidemiology, 1. 20,000 cases/yr; 1,000 deaths/yr 2. Radiation is well-established risk

Clinical Presentation, 1. Solitary thyroid nodule 2. “cold” or “hypofunctioning” on a radionuclide scan

Pathology, 1. 80% are papillary 2. Next most common is follicular 3. Medullary type associated with hypercalcemia (elevated calcitonin levels) and associated with MEN (multiple endocrine neoplasia) syndromes (e.g. pheochromocytoma, parathyroid adenomas) 4. Anaplastic type has worst prognosis 5. RET oncogene frequently mutated

Treatment, 1. Surgery and radioactive iodine ablation 2. Monitor recurrence with serum thyroglobulin levels 3. RET oncogene is a new therapeutic target

Breast and Gynecological Malignancies

Breast Cancer

Epidemiology 1. Most common cancer in N. American females 2. Second most common cause of cancer-related deaths in women 3. Increasing incidence with age (median age is 64) 4. Male breast cancer comprises <1% of all cases 5. Genetic factors: first degree relative with breast cancer increases risk, hereditary breast cancer syndromes (eg., BRCA 1 and 2, Li-Fraumeni syndrome, Lynch syndrome) 6. BRCA 1 increases risk for breast, colon, ovarian and prostate cancers 7. BRCA 2 increases risk for breast cancer (including male breast cancer) and pancreatic cancers (lower risk for ovarian cancer compared with BRCA 1) 8. The vast majority (90%) of cases of breast cancer are “sporadic” 9. Endocrine risks: prolonged endogenous estrogen from early menarche, late parity, nulliparity or late menopause increases risk. Small increased risk with post-menopausal hormone replacement therapy (greatest with combined estrogen and progesterone), but not with oral contraceptives 10. High fat diet, obesity, alcohol consumption, and possibly smoking are other risk factors 11. Ionizing radiation increases risk (in developing years) 12. History of atypical hyperplasia increases risk 4-5X 13. LCIS/DCIS increases risk 8-10X

Screening 1. Monthly breast self-exam (not proven to improve on mortality) 2. Yearly MD exam 3. Annual mammograms over the age 50 up to age 70 4. Mammograms prior to age 50 and over age 70 less proven 5. High risk women should have mammograms or MRI at an earlier age 6. MRI may be better in high risk women, including those with BRCA mutations; MRI is more sensitive than Mammography but MRI also has a high false positive rate

Clinical Presentation 1. Painless palpable mass 2. Asymptomatic non-palpable mammogram abnormality 3. Unilateral nipple discharge, nipple retraction, breast edema, breast dimpling, axillary or supraclavicular mass or pain 4. Tumor spread to regional lymph nodes is common (axillary) 5. Metastatic symptoms: cough, hemoptysis, dyspnea, bone pain, neurologic symptoms, weight loss

Work-up 1. Mammogram of both breasts 2. A “negative” mammogram in the face of a suspicious palpable mass should be pursued with an ultrasound and/or tissue diagnosis 3. FNA or core biopsy or excisional biopsy for diagnosis 4. All tumors should be evaluated for hormone status (ER, PR) and the presence of Her-2-neu overexpression; these have both prognostic significance and clinical implications

Pathology, 1. Non-invasive include ductal carcinoma in situ (DCIS) which is a pre-cursor to invasive cancer; frequently accompanies invasive cancer; lobular carcinoma in situ (LCIS) is not cancer but indicates a high risk and carries an equal risk in either breast 2. Invasive forms include adenocarcinomas that are derived from a breast gland duct (infiltrating ductal carcinoma) or milk producing cell (infiltrating lobular carcinoma); 80% are infiltrating ductal carcinoma 3. Other less common invasive types include medullary carcinoma (5%) which grow larger and are well circumscribed; they carry a better prognosis 4. Most aggressive and lethal form is inflammatory breast cancer; manifests as skin redness and warmth, induration of the underlying breast; cells infiltrate and obstruct subdermal lymphatics

Treatment, 1. Lumpectomy plus radiation is equivalent to modified radical mastectomy (MRM) 2. Adjuvant chemotherapy for larger tumors or locally advanced disease 3. Hormonal therapy for ER positive tumors (either in the adjuvant setting or for metastatic disease) 4. Anti-Her-2 therapy for tumors that are Her-2 positive (either in the adjuvant setting or for metastatic disease)

Ovarian Cancer

Epidemiology 1. Number one cause of death from a gynecologic malignancy in the US 2. 90% are sporadic case 3. One family member with ovarian cancer increases risk in women of that family to 5% (vs 1.5% for general population). However, in women with hereditary ovarian cancer, defined as multiple members with ovarian cancer alone or with breast cancer, the lifetime risk is 50%. 4. 80% of hereditary ovarian cancers are due to BRCA 1 with carriers having a > 50% lifetime risk of developing ovarian cancer 5. Risk with BRCA 2 mutation is much lower 6. Can be part of Lynch syndrome (DNA mismatch repair defect such as MSH2) 7. Risk decreases with the number of children one has (incessant ovulation hypothesis; ovulation requires repair and proliferation of surface epithelial cells) 8. Prolonged use of oral contraceptives also leads to a decrease risk (as much as 50%) 9. Role of prophylactic oopherectomy for women with hereditary ovarian cancer (90% risk reduction!); removal of ovaries i

Screening and prevention 1. False positive tests are common. Screening might be considered for only those at the highest risk (familial inheritance). 2. Trans-vaginal ultrasound and CA 125 screening in high risk individuals 3. Prophylactic oopherectomy may be considered in high risk individuals (also decreases risk for breast cancer).

Clinical Presentation 1. 95% of patients report symptoms prior to diagnosis; these symptoms may be vague and non-gynecologic; 75% present with advanced disease 2. Abdominal pain, fullness, distention, ascites 3. N/V due to GI obstruction, change in bowel habits 5. Premenopausal adnexal mass is usually a cyst (7% cancer) that regresses over time; postmenopausal adnexal mass is more like to be cancer (30%) 6. Many ovarian cancers will spread by direct exfoliation of cells onto the peritoneal surfaces and follow path of peritoneal fluid into pericolic gutter and hemidiaphragm

Work-up 1. CA 125 tumor marker is frequently elevated; however, it is not a specific marker for ovarian cancer since it is elevated in a number of other malignancies and benign conditions (e.g. Endometriosis). 2. With a suspicious pelvic mass, laparotomy is needed 3. Surgical staging is mandatory and must be comprehensive including multiple and numerous peritoneal biopsies, cytologic evaluation of peritoneal fluid, omentectomy, pelvic and para-aortic lymphadenectomy (minimal residual disease is < 2 cm largest nodule after debulking) 4. AFP and b-HCG if suspect germ cell tumors (rare) in a younger woman

Pathology 1. In contrast to primary tumors of the testis (which are predominately of germ cell origin), tumors of the ovaries are usally of epithelial origin (90%); Clear cell type has a worse prognosis. 2. <1% occur in women < 30 years of age and these are usually germ cell tumors 3. The volume of residual disease after cyto-reduction has prognostic significance 4. Primary peritoneal carcinomas can develop in women without ovaries; women with BRCA mutations are still at risk for this 5. “Low malignant potential” (LMP) tumors occur in a single ovary, usually confined, in pre-menopausal women; cells don’t usually become cancerous 6. Metastatic tumors to the ovary can occur (Krukenberg tumors), usually arising from the stomach, colon, breast and typically spreading to both ovaries

Treatment 1. Oopherectomy for early stage disease 2. Surgical debulking for more locally advanced and advanced disease 3. Chemotherapy for locally advanced and advanced disease; chemo can be given IV and sometimes given intra-peritoneal 4. Cure rates are high for stage I and II tumors; stage III and IV disease are much less curable (in contrast to germ cell tumors of the testis, whereby advanced disease is still highly curable).

Cervical Cancer

Epidemiology, 1. Low socioeconomic status and minorities at higher risk because of decreased rate of pelvic examinations 2. Similar to epidemiology of venereal disease (early coitus, frequent coitus, multiple sexual partners, poor genital hygiene) 3. Smoking and sexual promiscuity increases risk 4. AIDS defining illness in HIV carriers 5. HPV 16 and 18 infection occurs in 90% of invasive squamous cell cervical cancers

Screening/prevention, 1. Pelvic exam and Papanicolaou (Pap) smear highly effective for diagnosis of precursor disease (ASGUS, CIS). 2. Nearly 100% preventable by use of Pap smear 3. Most disease diagnosed as preinvasive and can be cured with surgery 4. 93% reduction in deaths from cervical cancer between 1950 and now where Pap smear is widely available 5. HPV vaccine for strains 6,11,16,18 will reduce risk of cervical cancer (and perhaps other HPV-related cancers such as some H/N cancers)

Clinical Presentation, 1. Vaginal bleeding or discharge 2. Pelvic pain 3. Inguinal lymphadenopathy

Work-up, 1. Pelvic exam and culposcopic biopsy 2. Abdominal and pelvic imaging (MRI) can assess spread

Pathology, 1. >80% are ecto-cervical squamous cell in origin 2. 20% are adenocarcinomas 3. Multi-step process: atypical cells -->low grade dysplasia--> high grade dysplasia-->carcinoma in situinvasive cancer

Treatment, 1. LEEP procedure or conization to surgically remove cancer precursor lesions 2. Small tumors are treated with hysterectomy 3. Larger tumors or locally advanced are treated with chemoradiation

Endometrial Cancer

Epidemiology, 1. Most common gynecological cancer 2. Occurs in predominately perimenopausal and postmenopausal women, many of whom are obese, diabetic, or a combination of these. 3.Unopposed estrogen stimulation of the endometrium is responsible for the development of endometrial cancer and can result from endogenous hormonal imbalance or exogenous use of unopposed estrogens; other hyperestrogen states such as obesity, polycystic ovaries, nulliparity, early menarche, late menopause are risks 3. Endometrial hyperplasia carries a 30% risk of transition to endometrial cancer 4.Use of tamoxifen for breast cancer is a risk for endometrial cancer; women on tamoxifen must get regular GYN exams 5. Most common extra-colonic tumor of the Lynch Syndrome

Screening, 1. No particular screening strategy other than the thorough investigation of perimenopausal or postmenopausal bleeding has been shown to be of valu

Clinical Presentation, 1. Classically presents as abnormal perimenopausal bleeding or any postmenopausal bleeding. 2.Early stage is the rule, since the tumors bleed at a limited stage of development

Pathology, 1. Most cases are adenocarcinoma (95%) 2. Papillary serous and clear cell carcinomas exhibit a poorer prognosis

Treatment, 1. Total abdominal hysterectomy is curative in most women 2. Some role for chemotherapy for advanced disease 3. hormonal therapy for ER-positive tumors

Gastrointestinal Malignancies

Esophageal Cancer

Epidemiology, 1. Increase in adenocarcinoma type in the US at an alarming rate, significant decrease in squamous cell type in the US 2. Squamous cell type related to tobacco and alcohol consumption 3. Predisposing conditions include tylosis, plummer-vinson syndrome, caustic injury, achalasia, H. pylori infection, possibly HPV, Barretts esophagus 4. Barrett’s esophagus is associated with a 30 fold increase in risk of esophageal adenocarcinoma

Work-up, 1. Upper endoscopy (EGD) for diagnosis 2. EUS for diagnosis/staging lymph node status and better at assessing T status than CT 3. PET is standard 4. CT chest (poor at assessing primary tumor and regional nodes) and abdomen 5. Brain and bone imaging only if clinically suspected (CNS symptoms, bone pain, elevated calcium or alkaline phosphatase)

Clinical Presentation, 1. Because it lacks a serosal coat, the esophagus is able to distend to accommodate considerable intraluminal tumor growth before symptoms occur 2. Dysphagia and weight loss are the initial symptoms in 90% of cases 3. Odynophagia, retrosternal pain, cough, hoarseness

Pathology, 1. Most common type in the US is adenocarcinoma followed by squamous cell carcinoma 2. Significant geographic variability world-wide

Treatment, 1. Surgery for stage I tumors (EMR—endoscopic mucosal resection for high grade dysplasia in patient not a surgical candidate) 2. Chemotherapy and radiation have a role in locally advanced disease

Gastric Cancer

Epidemiology, 1. Adenocarcinoma of the stomach has been the leading cause of cancer death worldwide through most of the 20th century 2. Now ranks second world-wide to lung cancer in overall incidence 3. Incidence in the US has decreased dramatically over the last century; however, the number of GE junction tumors has increased over the last 20 years (may be managed as either esophageal cancers or gastric cancer). The decreased incidence is due to better food preservation (refrigeration reduces bacterial and fungal contamination) 4. Highest incidences in Japan, South America, Eastern Europe, and portions of the Middle East 5. Associated with nutritional factors such as high nitrate consumption, high salt consumption, associated with EBV, H Pylori, pernicious anemia, Li-Fraumeni syndrome, and Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

Clinical Presentation, - Most patients are diagnosed with advanced stage disease with vague, nonspecific symptoms - Weight loss, fatigue, anorexia, epigastric pain, UGI bleeding; Anemia is common - All gastric ulcers must be biopsied to rule out malignancy - Unique clinical behavior---mets to ovaries, periumbilical area, Virchow’s node (left supraclavicular); associated with explosion of seborrheic kersatosis

Work-up, - Upper endoscopy (EGD) - EUS to stage regional lymph nodes - CT chest and abdomen - Role of PET is evolving

Pathology, - Adenocarcinoma comprises nearly100% of all cases - Intestinal type (more common) and diffuse type (cancer without a mass) - Diffuse type in extreme is linitis plastic - Familial form associated with Familial Adenomatous Polyposis (FAP) and HNPCC - FAP is related to a germ-line mutation of APC (adenomatous polyposis coli) gene - HNPCC is related to a germ-line mutation of DNA mismatch repair enzymes such as MSH2

Treatment, 1. Gastrectomy for early stage disease 2. Chemotherapy and/or radiation for locally advanced disease (with surgery) 3. Anti-Her-2 therapy for patients with advanced disease with tumors that are Her-2 +

Colorectal Cancer

Epidemiology, Second leading cause of cancer death overall when combining men and women, Genetic risks: Familial adenomatous polyposis (FAP), Hereditary non-polyposis colorectal cancer syndrome (HNPCC); there are also less common ones; untreated FAP results in nearly 100% risk of developing colon cancer in lifetime., APC gene mutations (tumor suppressor gene) common in familial syndromes (such as FAP) and sporadic cases. 80% of sporadic cases of colon cancer also have the APC gene mutation. Colon cancers usually arise from polyps: hyperplastic polyps do not carry a risk; tubular adenomas low risk; tubulovillous adenomas higher risk, villous adenomas highest risk., HNPCC clinical (Amsterdam) criteria: FAP excluded, at least 3 affected relatives, 2 of which are first degree relatives; the affected individuals must be from at least 2 successive generations; at least one of the individuals must have developed colon cancer before the age of 50; due to germ-line mutation of DNA mismatch repair enzymes such as MSH2, Lynch syndrome includes extra-colonic tumors such as endometrial cancer, gastric, ovarian, pancreatic, breast, others, Diet risks: low fiber and high fat may increase risk, Inflammatory bowel disease (Ulcerative colitis and Crohn’s disease) increases risk NSAID use and calcium use may be preventative in some persons

Clinical Presentation, 1. Found at screening colonoscopy or occult blood in stool 2. Constipation, anemia, abdominal pain, weight loss 3. Right sided tumors more commonly present with anemia 4. Left sided tumors more commonly present with obstructive symptoms

Work-up, 1. Screening with yearly stool hem-occult test for blood and sigmoidoscopy or colonoscopy (or barium enema) 2. Colonoscopy and biopsy 3. Abdominal CT to assess mass, local nodes, liver for mets.

Pathology, 1. Adenocarcinoma is the single histologic type

Treatment, 1. Surgery for early stage disease 2. Surgery followed by chemotherapy for stage III disease (LN involvement) 3. Chemotherapy for advanced disease (palliative)

Pancreatic Cancer

Epidemiology, 1. Most common documented risk is smoking 2. Dietary factors implicated 3. Chronic pancreatitis and diabetes are variably associated 4. BRCA-2 is a risk

Clinical Presentation, 1. The lack of obvious clinical signs and symptoms delay diagnosis in most patients 2. Jaundice due to extrahepatic biliary obstruction is present in 50% of patients at diagnosis 3. Dull, constant mid abdominal pain, fatigue, weight loss, anorexia 4. Glucose intolerance, pancreatic insufficiency

Work-up, 1. CT abdomen dual-phase 2. ERCP for diagnosis and stenting biliary duct if obstructed 3. EUS may assist in staging in some cases 4. Resectability should be determined: depends on proximity to major vessels, nerves, organs

Pathology, 1. The predominant histology is adenocarcinoma (exocrine cells) 2. Islet cell tumors (endocrine cells) and other tumors much less common

Treatment, 1. Whipple procedure (pancreatectomy, s. bowel resection, splenectomy, cholecystectomy) if surgically resectable 2. Chemotherapy and/or radiation for locally advanced tumors

Hepatocellular Carcinoma

Epidemiology, 1. Over 600,000 cases each year (globally) 2. Most common in Eastern Asia 3. Leading cause of cancer-related death in cirrhotic patients 4. Associated with cirrhosis, chronic liver disease, Hepatitis B and C; other risks include aflotoxins from aspergillus fungi in food

Clinical Presentation, 1. Enlarged, irregular/nodular liver 2. Hepatic bruit 3. Cachexia, fevers 4. Paraneoplastic syndromes include hypoglycemia due to ectopic production of IGF-2

Pathology, 1. Hepatoma or Fibrolamellar form (usually not associated with cirrhosis; better prognosis; higher incidence in women) 2. Can be multifocal, nodular, or encapsulated tumor

Treatment, 1. Liver resection can be curative 2. Liver transplantation if liver function not acceptable for resection 3. Chemoembolization procedure to shrink cancer, reduce symptoms if residual liver function is sufficient 4. Resistant to chemotherapy and radiation therapy 5. Treat advanced disease with angiogenesis inhibitor

Genitourinary Malignancies

Bladder Cancer

Epidemiology, 1. Most cases are preventable: Tobacco usage increases risk (causes 1/3-1/2 of cases); other risks include: exposure to aromatic amines from the rubber industry and prior cyclophosphamide 2. Schistosoma haematobium is associated with squamous cell carcinoma of the bladder

Clinical Presentation, 1. Painless MACROSCOPIC hematuria (80%) 2. Urinary frequency, dysuria 3. Weight loss, bone pain from mets

Work-up, 1. Cystoscopy with biopsy 2. Urine cytology 3. Bone scan if symptoms warrant 4. Abdominal imaging

Pathology, 1. 90% are transitional cell in origin and are now called high grade urothelial carcinoma 2. Tumors may be superficial, muscle invasive, locally advanced, or metastatic 3. Recurrences from superficial bladder cancer are common

Treatment, 1. Superficial cancers are treated by transurethral resection and subsequent intra-bladder installation of chemicals (BCG, chemotherapy) 2. Muscle invasive tumors requires a cystectomy (or radiation in some patients) 3. Chemotherapy is frequently given with surgery and is also used in metastatic setting

Renal Cell Cancer

Epidemiology, – Tobacco is a major risk factor; other risk factors include obesity, long-term dialysis – Von Hipple Lindau disease has a 25% incidence of renal cell cancer; this is a rare, autosomal dominant disease that results in multiple, bilateral renal cancers at a younger age; also at risk for other tumors: pheochromocytoma, hemangioblastomas, retinal angiomas (VHL gene sporadically mutated in most cases of renal cancer)

Clinical Presentation, – MICROSCOPIC hematuria, flank pain, flank mass (Classic Triad) – Multiple paraneoplastic syndromes may occur such as hypertension (increased renin), ectopic ACTH, erythrocytosis (increased erythropoietin), hypercalcemia, amyloidosis – Weight loss, fevers – Interesting clinical behavior which appears immune-mediated; removal of primary kidney tumor can result in regression of mets

Work-up, 1. Urinalysis 2. Intravenous pyelogram (IVP) 3. CXR to rule out pulmonary mets 4. CT abdomen and pelvis

Pathology, 1. 90% are adenocarcinomas 2. Spread first occurs via local extension into adrenal glands, to regional lymph nodes, and into the renal vein 3. Hematogenous metastasis is common, with most common sites being the lung and liver (and less commonly bone)

Treatment, 1. Nephrectomy can be curative for organ confined disease 2. Sensitive to immune modulation (IL-2) and newer targeted agents (e.g. angiogenic inhibitors) 3. Relatively resistant to chemotherapy and radiation

Male Malignancies

Testicular Cancer

Epidemiology, - Most common cancer in males age 15-35; 95% arise from germ cells - Risk factor: cryptorchidism, which is an undescended testis found at birth (10% of cases); risk of cancer in either testis - Other primary sites for germ cell cancers include the anterior mediastinum and the retroperitoneum - Risk factor for primary mediastinal GCT is Klinefelters’ Syndrome - 80% are oligospermic at the time of diagnosis; 10% are infertile; consider sperm banking prior to chemotherapy

Clinical Presentation, – Painless scrotal mass – Most commonly presents as stage I (confined to the testis) – Back pain due to retroperitoneal lymphadenopathy – Pulmonary symptoms due to lung metastases – Teratoma grows by local extension and can “transform into other cancers” – Non-teratomatous forms of germ cell cancer spread via lymphatics and hematogenously (primarily to the lungs)

Work-up, – Scrotal ultrasound revealing a hypoechoic mass; never perform a transcrotal biopsy – Orchiectomy is usually performed for diagnosis/treatment – AFP, b-HCG; CT chest/abdomen – Associated with Chromosome i12p

Pathology, – Divided into seminoma and non-seminoma – Non-seminoma comprised of 4 types: choriocarcinoma, embryonal carcinoma, yolk sac tumor and teratoma – Choriocarcinoma secretes b-HCG, yolk sac tumor secretes AFP; embryonal carcinoma secretes both and teratoma secretes neither – Seminomas may secrete low levels of b-HCG, but NEVER secrete AFP – B-HCG can be falsely elevated in marijuana users

Prognostic Variables, 1. 90% are curable; poor risk variables include AFP > 10,000; b-HCG > 50,000; primary mediastinal non-seminomatous tumor; bone, brain, or liver mets

Treatment, 1. Orchiectomy usually curative in stage I disease 2. Highly chemotherapy sensitive (except teratoma) and highly curable even in advanced stage 3. Surgery to remove distant mets and remove residual radiographic abnormalities after chemotherapy 4. Teratoma must be surgically removed (neither chemotherapy nor radiation-sensitive) 5. Radiation may play a role in some patients with pure seminoma

Prostate Cancer

Epidemiology, 1. Most common cancer (after skin cancer) in males 2. Age and African-American race increase risk 3. Family history increases risk 4. Testosterone is permissive but not causative

Clinical Presentation, 1. 10% asymptomatic finding at TURP for benign prostatic hypertrophy (BPH) 2. Rising PSA on yearly screening (most common); rate of increase of PSA (PSA velocity) may be helpful in characterizing risk of elevated PSA being due to cancer 3. Urinary obstructive symptoms such as hesitancy, frequency, nocturia, or complete outlet obstruction 4. Back or hip pain from mets

Work-up, 1. Transrectal ultrasound and biopsy (do cores from 6-12 locations) 2. Creatinine to assess renal function, calcium and alkaline phosphatase 3. PSA 4. Abdominal/pelvic CT to assess regional node status 5. Bone scan

Pathology, 1. 75% occur in the peripheral zone of the posterior lobe, often palpable on rectal exam 2. Almost all are adenocarcinomas 3. Aggressiveness of morphology and differentiation is graded 2-10 on Gleason’s score 4. Spread to regional lymph nodes 5. Distant mets most commonly to bone, then lung, liver, and adrenal glands

Treatment, 1. Highly sensitive to medical or surgical castration 2. Surgery and Radiation are equally curative in organ-confined disease 3. Modestly chemotherapy-sensitive 4. Prostate cancer vaccine FDA approved to treat metastatic disease 5. Watchful waiting is appropriate for many older patients with co-morbidities and early stage disease

Head and Neck Malignancy

Head/Neck Cancer

Epidemiology, 1. Tobacco usage is the major risk factor, followed by alcohol (cofactor) 2. Asbestos, heavy metal exposure, and radiation exposure also increase risk 3. Nasopharyngeal carcinoma are associated with EBV infection 4. Emerging role for HPV (better prognosis)

Clinical Presentation, 1. Oral or neck mass, pain 2. Cough, dysphagia 3. Hoarseness 4. Weight loss 5. Cranial nerve deficits 6. Unilateral otalgia or otitis

Work-up, 1. Laryngoscopy with biopsy 2. Head/neck CT/ MRI 3. CXR to rule out pulmonary mets and to assess for separate primary lung cancer 4. PET, Bone scans in some instances 5. Tobacco cessation 6. Dental Consultation

Pathology, 1. May originate from sinuses, oral cavity, pharynx, larynx, salivary glands 2. Usually squamous cell in origin 3. Salivary gland tumors are usually adenocarcinomas, but may be adenoid cystic 4. Nasopharyngeal carcinomas are more commonly squamous cell in N. America and more commonly lymphoepithelioma in Asian populations

Treatment, 1. primary treatment is surgery and radiation 2. chemotherapy may be included for locally advanced or metastatic disease

Skin Malignancy

Melanoma

Epidemiology, 1. Intermittent high exposure to the sun during childhood is a major risk factor 2. Other risk factors include a family history of melanoma, increased number of nevi, and xeroderma pigmentosum 3. Melanoma can be inherited, familial atypical multiple mole (FAMM) syndrome, caused by inherited mutation in p16

Clinical Presentation, 1. Most commonly in the lower extremities in women and back in men. Trunk presentations are poorer prognosis 2. Characteristic malignant nevi include variation in color with the nevus, irregular raised surface, irregular perimeter, bleeding and ulceration (bad prognostic sign) 3. ABCD of melanoma presentation: asymmetry, border irregularity, color variation, diameter larger than 6 mm 4. High propensity for brain mets and also to unusual sites (e.g. small bowel)

Work-up, – If stage I, no further work-up necessary – For thickness of nevus greater than 2 mm into skin, regional lymph node assessment with sentinel nodal biopsies – If extension below the epidermis or a local lymph node is positive, bone scan and imaging of chest and abdomen may be necessary

Pathology, – Four major types: superficial spreading (most common and best prognosis), nodular (most likely to metastasize), lentigo, and acral lentigous (palms/soles, nails) – Spread occurs first to local and then regional lymph nodes. Hematogenous spread to multiple organs with bizarre manifestations can occur. Metastatic disease may be rapidly fatal or have spontaneous remissions – Melanoma can occur wherever there are pigment cells, including the eye. Ocular melanoma is often curable – Thickness of lesion (Breslow’s score) determine the prognosis: <1.5 mm is good, >4 mm is bad

Treatment, 1. Surgical resection with wide margins is usually curative 2. Responsive to some immunotherapy including a vaccine therapy 3. Nearly ½ harbor a BRAF mutation and are highly sensitive to a BRAF inhibitor 4. Modestly chemotherapy-sensitive; relatively radiation resistant

CNS Malignancy

Primary CNS Tumors

Risk Factors:, 1. Radiation exposure, 2. Familial syndromes including neurofibromatosis, Von-Hippel Lindau, and Li-Fraumeni

Pathology, 1. Childhood: medulloblastomas, low grade astrocytomas, ependymomas 2. Adult: high grade astrocytomas, usually glioblastoma multiforme (GBM) 3. Grade of tumor determines aggressiveness (I-IV)

Clinical Presentation, 1.Present with CNS symptoms (headaches, nausea, seizures) or metabolic (DI/SIADH) 2.Specific symptoms may occur depending upon the location of the primary (frontal tumors may cause mental status changes, labile behavior; temporal lobe tumors may cause hallucinations, speech or hearing abnormalities; occipital lobe tumors may cause visual deficits; cerebellar tumors may cause nystagmus or ataxia; brain stem tumors may cause CN deficits) 3. metastases to brain is common from many other primary sites including brain, breast, melanoma, and renal cancer 4. metastases to spine causing spinal cord compression is not uncommon; the first sign of a spinal cord compression is new or worsening back pain

Treatment, 1. Low grade tumors may be observed if symptoms such as seizures are well controlled 2. High grade tumors are frequently incurable---debulking surgeries frequently performed followed by whole brain radiation 3. Some role for chemotherapy in advanced disease 4. Anti-angiogenic agents have an emerging role against GBM 5. Steroid use (e.g. dexamethasone) plays a critical role in reducing edema around tumor and decreasing intracranial pressure (reduces headaches, seizures, other symptoms of disease)

Other

Sarcomas

Epidemiology, - Bone and soft tissue sarcomas are uncommon - There are 750 new cases of osteosarcoma, 450 new cases of chondrosarcoma, 250 cases of Ewings Sarcoma and 6000 new cases of soft tissue sarcomas annually - Osteosarcomas are present in various anatomic locations - Soft tissue sarcomas occur most commonly in the extremities, retroperitoneum and head/neck - Associated with loss of p53 and RB tumor suppressor genes - Associated with radiation exposure - Associated with Li-Fraumeni syndrome (loss of p53)

Clinical Presentation, - Localized pain and swelling is the hallmark of bone sarcomas - Symptoms and signs according to location of tumor and extent of disease

Work-up, - Bone biopsies should be done with great care under the supervision of the treating orthopedic surgeon - Bone scans useful for detecting occult mets - CT/MRI imaging of extremity tumors

Treatment, 1. Surgery is the mainstay of therapy 2. Chemotherapy plays an important role in osteosarcomas and some other sarcomas 3. Molecularly targeted agents show promise against some sarcomas (e.g. IGF inhibitors; c-kit inhibitors; RANK ligand inhibitors)