question_Oncology

Educational objective: review of imaging modalities for examination of bone affected with multiple myeloma.

Conventional roentgenograms reveal punched-out lytic lesions of the bone, osteoporosis, or fractures in almost 80% of patients with multiple myeloma at diagnosis. The most commonly affected areas are vertebra, skull, thoracic cage, pelvis and proximal humeri and femora. Rechnetium-99m bone scanning is inferior to conventional x-rays for the detection of lytic lesions and should not be used for this purpose (it is, however, excellent for detection of osteoblastic lesions).

CT scanning and MRI may be helpful in patients who have bone pain but no abnormalities on conventional x-rays (MRI also may have prognostic value). These methods should not be used for initial evaluation.

Educational objective: Review cancers associated with CEA.

CEA is associated with colorectal, gastric, pancreatic, breast, lung, bladder, ovarian, and prostate malignancies; whereas hepatocellular carcinoma and choriocarcinoma are associated with alpha fetoprotein and beta HCG markers respectively.

Educational objective: Review associations between development of new malignancies and use of anticancer drugs.

Both cyclophosphamide and melphalan can cause leukemia and bladder cancer. Thorotrast has been implicated in causing angiosarcoma of the liver. Although used in breast cancer, tamoxifen can cause endometrial carcinoma.

Educational objective: Review features and significance of Eaton-Lambert syndrome.

Symptoms in this man are consistent with Eaton-Lambert syndrome. This syndrome shares the same pathologic site with myasthenia gravis (the neuromuscular junction) and has a similar path physiology (an autoimmune disease). Eaton-Lambert syndrome is usually associated with malignancy. Up to 70% of these patients have associated small cell lung cancer, and this disease must be ruled out in every patient with presenting symptoms of Eaton-Lambert syndrome.

Clinical presentation of the Eaton-Lambert syndrome includes weakness that is typically seen early in the hip girdle, making it difficult for the patient to rise from a chair or to climb the stairs. Less dramatic is shoulder girdle weakness. Involvement of the bulbar muscles or diplopia is rare, but ptosis is frequently seen. Symptoms are also likely to be more prominent in the morning; autonomic dysfunction may cause erectile dysfunction and dry mouth.

Differentiation from myasthenia gravis may be hard since patients with Eaton-Lambert syndrome have a positive AChR-Ab test in 13% of cases.

Educational objective: Review clinical features and diagnostic procedures for Lambert-Eaton syndrome.

Lambert-Eaton syndrome shares the same pathologic site with myasthenia gravis (the neuromuscular junction) and has a similar pathophysiology (an autoimmune disease). Lambert-Eaton syndrome is usually associated with malignancy. Up to 70% of patients have associated small cell lung cancer, and this disease must be ruled out in every patient with the presenting symptoms of Lambert-Eaton syndrome.

Clinical presentations of Lambert-Eaton syndrome include weakness that is typically seen early in the hip girdle, making it difficult for the patient to rise from a chair or to climb the stairs. Less dramatic is shoulder girdle weakness. Involvement of the bulbar muscles or diplopia is rare, but ptosis is frequently seen. Symptoms are also likely to be more prominent in the morning; autonomic dysfunction may cause erectile dysfunction and dry mouth.

Repetitive nerve stimulation at high rates (20-50 cycles per second) produces an increase in response, in contrast to the progressive weakness in myasthenia.

Over 95% of patients with Lambert-Eaton syndrome have antibodies against P/Q-type calcium channels. These antibodies are found in less than 5% of patients with myasthenia gravis.

Educational objective: Review different clinical syndromes occurring in association with malignant neoplasms.

Adenocarcinoma is the one lung cancer most commonly associated with hypertrophic osteoarthropathy (clubbed fingers, etc.) and bronchioalveolar carcinoma is often characterized by the production of a large amount of watery sputum. Squamous cell cancer often causes hypercalcemia and hypophosphatemia due to production of PTH or PTH-related peptides. Small cell lung cancer is associated with SIADH, secretion of the atrial natriuretic hormone and ACTH. Large cell lung cancer is associated with gynecomastia and galactorrhea.

Educational objective: Review different clinical syndromes occurring in association with malignant neoplasms.

Adenocarcinoma is the one lung cancer most commonly associated with hypertrophic osteoarthropathy (clubbed fingers, etc.), and bronchioalveolar carcinoma is often characterized by the production of a large amount of watery sputum. Squamous cell cancer often causes hypercalcemia and hypophosphatemia due to production of PTH or PTH-related peptides. Small cell lung cancer is associated with SIADH, secretion of the atrial natriuretic hormone and ACTH. Large cell lung cancer is associated with gynecomastia and galactorrhea.

Educational objective: Review different clinical syndromes occurring in association with malignant neoplasms.

Adenocarcinoma is the one lung cancer most commonly associated with hypertrophic osteoarthropathy (clubbed fingers, etc.) and bronchioalveolar carcinoma is often characterized by the production of a large amount of watery sputum. Squamous cell cancer often causes hypercalcemia and hypophosphatemia due to production of PTH or PTH-related peptides. Small cell lung cancer is associated with SIADH, secretion of the atrial natriuretic hormone and ACTH. Large cell lung cancer is associated with gynecomastia and galactorrhea.

Educational objective: Review different clinical syndromes occurring in association with malignant neoplasms.

Adenocarcinoma is the one lung cancer most commonly associated with hypertrophic osteoarthropathy (clubbed fingers, etc.) and bronchioalveolar carcinoma is often characterized by the production of a large amount of watery sputum. Squamous cell cancer often causes hypercalcemia and hypophosphatemia due to production of PTH or PTH-related peptides. Small cell lung cancer is associated with SIADH, secretion of the atrial natriuretic hormone and ACTH. Large cell lung cancer is associated with gynecomastia and galactorrhea.

Educational objective: Review different clinical syndromes occurring in association with malignant neoplasms.

Adenocarcinoma is the one lung cancer most commonly associated with hypertrophic osteoarthropathy (clubbed fingers, etc.) and bronchioalveolar carcinoma is often characterized by the production of a large amount of watery sputum. Squamous cell cancer often causes hypercalcemia and hypophosphatemia due to production of PTH or PTH-related peptides. Small cell lung cancer is associated with SIADH, secretion of the atrial natriuretic hormone and ACTH. Large cell lung cancer is associated with gynecomastia and galactorrhea.

The most common malignant tumors of the small intestine are adenocarcinoma (45%), carcinoid (34%) lieomyosarcoma (18%) and lymphoma 3%.

Painless mass in the scrotum is the most common presentation. Pain or discomfort is present in 25% of the cases. 20-50% of cases already have metastases at the time of diagnosis, most commonly to the retroperitoneal lymph nodes and then liver and lung.

Differential diagnosis includes epididymitis, hydrocele, inguinal hernia, hematocele, testicular torsion, scrotal hematoma, syphilitic gumma, varicocele and spermatocele. Tumor is highly curable (95% if no detectable metastases with orchiectomy and either retroperitoneal lymph nodes dissection or surveillance by serum hCG and AFP measurements as well as CXR, CT of the abdomen and physical examinations).

Patients with more advanced tumors and with relapses after initial therapy still can be cured in 98% of the cases by combination chemotherapy with etoposide and cisplatin with or without bleomycin.

In HIV infected patients lymphoma usually occurs when CD4+ count falls below 200/mL. Most are B-cell in origin and may contain Epstain-Barr virus DNA and be mono or oligoclonal. Approximately 80% of the lymphomas in HIV infected patients are high or intermediate grade and ¾ are large cell or immunoblastic. Primary CNS lymphoma accounts for about 20% and tend to occur at even lower CD4+ counts. Kaposi’s sarcoma occurs at a constant rate throughout the course of the illness. The median survival is about 10 months for systemic lymphomas and 2-4 months for primary CNS lymphomas in HIV infected patients.

Educational objective: Review the features of anaplastic thyroid cancer.

Anaplastic thyroid carcinomas are undifferentiated tumors of the thyroid follicular epithelium. Anaplastic carcinomas are very aggressive tumors with a disease-specific mortality approaching 100%. Early recognition is essential to allow prompt initiation of therapy and to maintain hope for significant response. The annual incidence of anaplastic carcinoma is about two per million persons.

Approximately 20% of patients with anaplastic carcinoma have a history of differentiated thyroid carcinoma, and another 20-30% has associated differentiated carcinoma. The great majority are papillary carcinomas, but follicular have been described.

Nearly all patients with anaplastic thyroid cancer present with a thyroid mass. However, the disease has already spread either locally in the neck or distantly in more than 90% of the cases. In the neck the affected structures include perithyroidal fat and muscle, lymph nodes, larynx, trachea, esophagus, tonsil, and great vessels. Distant metastases are found in 15-50% of the patients. The lungs are the most common site of distant metastases (90% of the patients with distant disease). Other sites of metastases are bone, brain and skin. Symptoms include neck pain and tenderness, compression (and invasion) of upper airways with dyspnea (35%), dysphagia (30%), hoarseness (25%), cough (25%). Less common symptoms are chest pain, bone pain, headache, confusion, or abdominal pain from metastases. All other options are highly unlikely.

Educational objective: Review relative ratios of different thyroid carcinomas.

-Approximate frequency of malignant thyroid tumors Papillary carcinoma 75% Follicular carcinoma 16% Medullary carcinoma 5% Undifferentiated carcinoma 3% Miscellaneous (lymphoma, fibrosarcoma squamous cell,hemangioendotelioma, teratoma and metastatic cancers) 1%

Educational objective: Review therapeutic modalities for solitary metastasis to the bone.

Bone metastases are a common development in patients with carcinomas. The most appropriate and effective nonpharmacologic treatment of bone pain caused by localized bone metastasis is localized radiation therapy. Up to 90% of patients experience some degree of bone pain, and 1/2 to 2/3 have complete pain resolution. Hemibody irradiation is appropriate for patients with widespread metastases (this is commonly seen with prostate carcinoma, breast cancer and multiple myeloma). In patients who do not respond to radiation, administration of phosphorus 32 (have significant hematologic toxicity) or strontium 89 may be attempted.

Educational objective: Review prognostic factors and pathologic staging of colonic cancer.

Prognosis is the most dependent upon pathologic stage at the time of resection. The five-year survival for each stage is as follows:

• A - 97%
• B1- 78%
• B2- 78%
• C1- 74%
• C2- 48%
• A - 4%

Astler-Coller modification of Dukes’ staging system for colorectal cancer:

• A- Tumor confined to mucosa, above the muscularis propria, no involvement of lymph nodes
• B1- Into muscularis propria but above pericolic fat, no involvement of lymph nodes
• B2- Into pericolic or perirectal fat, no involvement of lymph nodes
• C1- Same penetration as B1, but with nodal metastases
• C2- Same penetration as B2, but with nodal metastases
• D- Distant metastases

There is no relation of prognosis and size of primary tumor; effect of pathohistologic type and location of tumor are much more modest than those of stage. able in this case since they would just delay appropriate therapy.

Educational objective: Review appropriate management of patients with colonic polyps.

All polyps discovered by the screening sigmoidoscopy should be biopsied (or removed if possible). If the lesions found prove to be adenomatous adenomas or cancerous, the patient should be offered colonoscopy to remove polyps, treat limited cancerous lesions definitively, and examine the entire colon and rectum for synchronous neoplasms. Patients who have tubular adenomas smaller than 5 mm should make a decision (guided by physician) whether or not to undergo colonoscopy.

Educational objective: Review the role of CEA in management of patients with colon cancer.

The only laboratory test recommended for routine colorectal cancer surveillance is carcinoembryonic antigen (CEA). This is an oncofetal protein that is often elevated in patients with colorectal cancer (about 70%). It is not useful as a tool for primary screening because of low sensitivity and specificity. However in patients with established colorectal cancer, CEA may be used to detect relapse (and even to determine prognosis to some extent). Most patients with colorectal cancer and elevated CEA have a decrease in CEA postoperatively. A rising CEA concentration after resection may be used as a sign of local recurrence or liver metastases. The estimated sensitivity of the CEA to detect relapse is about 70%, but there is no data that shows that detection of relapse improves outcome. Alpha-fetoprotein and liver function tests are not useful in detection of recurrence, and FOBT is used in primary screening of colorectal cancer but not in secondary surveillance.

Educational objective: Review recommendations for colorectal cancer screening.

The American cancer society recommendations for colorectal cancer screening are as follows:

1. Annual digital rectal exam beginning at age 40
2. Annual FOBT beginning at age 50
3. Flexible sigmoidoscopy every 3-5 years beginning at age 50

Patients at greater than average risk for colorectal cancer should undergo colonic surveillance which is individualized according to the risk of cancer:

1. Previous history of adenomatous polyps - once polyps are removed colonoscopy should be performed in 3years.
2. Previous history of colorectal cancer - colonoscopy 6 months to 1year after surgery, then in 3 years and if negative every 5 years thereafter.
3. Patients with familial adenomatous polyposis should undergo yearly flexible sigmoidoscopy beginning at puberty,
4. Patients with hereditary nonpolyposis colon cancer should undergo colonoscopy every 1-2 yrs beginning at age 25 or 10 yrs younger than the age of the youngest relative with colon cancer.
5. Patients with inflammatory bowel diseases (IBD) - colonoscopy is performed every 1-2 years after 8-10 years of pancolitis and after 15 years of left sided colitis.
6. People with a first-degree relative (parent, sibling, or child) with colon cancer or adenomatous polyps diagnosed at age <60 years or 2 first-degree relatives diagnosed with colorectal cancer at any age should be advised to have screening colonoscopy starting at age 40 years or 10 years younger than the earliest diagnosis in their family, whichever comes first, and repeated every 5 years (see Table 3 in the original guideline document).
7. People with a first-degree relative with colon cancer or adenomatous polyp diagnosed at age >60 years or 2 second-degree relatives with colorectal cancer should be advised to be screened as average risk persons, but beginning at age 40 years.
8. People with 1 second-degree relative (grandparent, aunt, or uncle) or third-degree relative (great-grandparent or cousin) with colorectal cancer should be advised to be screened as average risk persons.

Educational objective: review recommendations for colorectal cancer screening.

The American Cancer Society recommendations for colorectal cancer screening are as follows:

1. Annual digital rectal exam beginning at age 40
2. Annual FOBT beginning at age 50- yearly screening with fecal occult blood test (FOBT) using a guaiac-based test with dietary restriction or an immunochemical test without dietary restriction. Two samples from each of 3 consecutive stools should be examined without rehydration. Patients with a positive test on any specimen should be followed up with colonoscopy.
3. Flexible sigmoidoscopy every 3-5 yrs beginning at age 50
4. Colonoscopy every 10 years, beginning at age 50
5. Combined FOBT and Flexible Sigmoidoscopy -- screening with FOBT every year combined with flexible sigmoidoscopy every 5 years. When both tests are performed, the FOBT should be done first.
6. Double-contrast barium enema every 5 years

Patients at greater than average risk for colorectal cancer should undergo colonic surveillance which is individualized according to the risk of cancer:

1. Previous history of adenomatous polyps - once polyps are removed colonoscopy should be performed in 3 years.
2. Previous history of colorectal cancer - Colonoscopy 6 months to 1year after surgery, then in 3 years and if negative every 5 years thereafter.
3. Patients with familial adenomatous polyposis should undergo yearly flexible sigmoidoscopy beginning at puberty and counseling to consider genetic testing If the genetic test is positive, colectomy is indicated. These patients are best referred to a center with experience in the management of FAP.
4. Patients with hereditary nonpolyposis colon cancer should undergo colonoscopy every 1-2 years beginning at age 25- not correct – 21 years old or 10 years younger than the age of the youngest relative with colon cancer. They also have to be counseled to consider genetic testing. If the genetic test is positive or if the patient has not had genetic testing, colonoscopy is done every 1-2 years until age 40, then annually. These patients are best referred to a center with experience in the management of HNPCC.
5. Patients with inflammatory bowel diseases (IBD) - colonoscopy is performed every 1-2 years after 8-10 years of pancolitis and after 15 years of left sided colitis. Colonoscopy done with biopsies for dysplasia every 1-2 years. These patients are best referred to a center with experience in the surveillance and management of inflammatory bowel disease.
6. First degree relative with colon cancer diagnosed less than age 50 - Colonoscopy beginning at 35-40 years of age.— Colonoscopy at age 40, or 10 years before the youngest case in the immediate family, whichever is earlier, than colonoscopy every 5-10 years.

Educational objective: review recommendations for colorectal cancer screening.

The American Cancer Society recommendations for colorectal cancer screening are as follows:

1. Annual digital rectal exam beginning at age 40
2. Annual FOBT beginning at age 50- yearly screening with fecal occult blood test (FOBT) using a guaiac-based test with dietary restriction or an immunochemical test without dietary restriction. Two samples from each of 3 consecutive stools should be examined without rehydration. Patients with a positive test on any specimen should be followed up with colonoscopy.
3. Flexible sigmoidoscopy every 3-5 yrs beginning at age 50
4. CColonoscopy every 10 years, beginning at age 50
5. Combined FOBT and Flexible Sigmoidoscopy -- screening with FOBT every year combined with flexible sigmoidoscopy every 5 years. When both tests are performed, the FOBT should be done first.
6. Double-contrast barium enema every 5 years

Patients at greater than average risk for colorectal cancer should undergo colonic surveillance which is individualized according to the risk of cancer:

1. Previous history of adenomatous polyps - once polyps are removed colonoscopy should be performed in 3 years.
2. Previous history of colorectal cancer - Colonoscopy 6 months to 1year after surgery, then in 3 years and if negative every 5 years thereafter.
3. Patients with familial adenomatous polyposis should undergo yearly flexible sigmoidoscopy beginning at puberty and counseling to consider genetic testing If the genetic test is positive, colectomy is indicated. These patients are best referred to a center with experience in the management of FAP.
4. Patients with hereditary nonpolyposis colon cancer should undergo colonoscopy every 1-2 years beginning at age 25- not correct – 21 years old or 10 years younger than the age of the youngest relative with colon cancer. They also have to be counseled to consider genetic testing. If the genetic test is positive or if the patient has not had genetic testing, colonoscopy is done every 1-2 years until age 40, then annually. These patients are best referred to a center with experience in the management of HNPCC.
5. Patients with inflammatory bowel diseases (IBD) - colonoscopy is performed every 1-2 years after 8-10 years of pancolitis and after 15 years of left sided colitis. Colonoscopy done with biopsies for dysplasia every 1-2 years. These patients are best referred to a center with experience in the surveillance and management of inflammatory bowel disease.
6. First degree relative with colon cancer diagnosed less than age 50 - Colonoscopy beginning at 35-40 years of age.— Colonoscopy at age 40, or 10 years before the youngest case in the immediate family, whichever is earlier, than colonoscopy every 5-10 years.

Educational objective: review recommendations for colorectal cancer screening.

The American Cancer Society recommendations for colorectal cancer screening are as follows:

1. Annual digital rectal exam beginning at age 40
2. Annual FOBT beginning at age 50- yearly screening with fecal occult blood test (FOBT) using a guaiac-based test with dietary restriction or an immunochemical test without dietary restriction. Two samples from each of 3 consecutive stools should be examined without rehydration. Patients with a positive test on any specimen should be followed up with colonoscopy.
3. Flexible sigmoidoscopy every 3-5 yrs beginning at age 50
4. Colonoscopy every 10 years, beginning at age 50
5. Combined FOBT and Flexible Sigmoidoscopy -- screening with FOBT every year combined with flexible sigmoidoscopy every 5 years. When both tests are performed, the FOBT should be done first.
6. Double-contrast barium enema every 5 years

Patients at greater than average risk for colorectal cancer should undergo colonic surveillance which is individualized according to the risk of cancer:

1. Previous history of adenomatous polyps - once polyps are removed colonoscopy should be performed in 3 years.
2. Previous history of colorectal cancer - Colonoscopy 6 months to 1year after surgery, then in 3 years and if negative every 5 years thereafter.
3. Patients with familial adenomatous polyposis should undergo yearly flexible sigmoidoscopy beginning at puberty and counseling to consider genetic testing If the genetic test is positive, colectomy is indicated. These patients are best referred to a center with experience in the management of FAP.
4. Patients with hereditary nonpolyposis colon cancer should undergo colonoscopy every 1-2 years beginning at age 25- not correct – 21 years old or 10 years younger than the age of the youngest relative with colon cancer. They also have to be counseled to consider genetic testing. If the genetic test is positive or if the patient has not had genetic testing, colonoscopy is done every 1-2 years until age 40, then annually. These patients are best referred to a center with experience in the management of HNPCC.
5. Patients with inflammatory bowel diseases (IBD) - colonoscopy is performed every 1-2 years after 8-10 years of pancolitis and after 15 years of left sided colitis. Colonoscopy done with biopsies for dysplasia every 1-2 years. These patients are best referred to a center with experience in the surveillance and management of inflammatory bowel disease.
6. First degree relative with colon cancer diagnosed less than age 50 - Colonoscopy beginning at 35-40 years of age.— Colonoscopy at age 40, or 10 years before the youngest case in the immediate family, whichever is earlier, than colonoscopy every 5-10 years.

Educational objective: review recommendations for colorectal cancer screening.

The American Cancer Society recommendations for colorectal cancer screening are as follows:

1. Annual digital rectal exam beginning at age 40
2. Annual FOBT beginning at age 50- yearly screening with fecal occult blood test (FOBT) using a guaiac-based test with dietary restriction or an immunochemical test without dietary restriction. Two samples from each of 3 consecutive stools should be examined without rehydration. Patients with a positive test on any specimen should be followed up with colonoscopy.
3. Flexible sigmoidoscopy every 3-5 yrs beginning at age 50
4. Colonoscopy every 10 years, beginning at age 50
5. Combined FOBT and Flexible Sigmoidoscopy -- screening with FOBT every year combined with flexible sigmoidoscopy every 5 years. When both tests are performed, the FOBT should be done first.
6. Double-contrast barium enema every 5 years

Patients at greater than average risk for colorectal cancer should undergo colonic surveillance which is individualized according to the risk of cancer:

1. Previous history of adenomatous polyps - once polyps are removed colonoscopy should be performed in 3 years.
2. Previous history of colorectal cancer - Colonoscopy 6 months to 1year after surgery, then in 3 years and if negative every 5 years thereafter.
3. Patients with familial adenomatous polyposis should undergo yearly flexible sigmoidoscopy beginning at puberty and counseling to consider genetic testing If the genetic test is positive, colectomy is indicated. These patients are best referred to a center with experience in the management of FAP.
4. Patients with hereditary nonpolyposis colon cancer should undergo colonoscopy every 1-2 years beginning at age 25- not correct – 21 years old or 10 years younger than the age of the youngest relative with colon cancer. They also have to be counseled to consider genetic testing. If the genetic test is positive or if the patient has not had genetic testing, colonoscopy is done every 1-2 years until age 40, then annually. These patients are best referred to a center with experience in the management of HNPCC.
5. Patients with inflammatory bowel diseases (IBD) - colonoscopy is performed every 1-2 years after 8-10 years of pancolitis and after 15 years of left sided colitis. Colonoscopy done with biopsies for dysplasia every 1-2 years. These patients are best referred to a center with experience in the surveillance and management of inflammatory bowel disease.
6. First degree relative with colon cancer diagnosed less than age 50 - Colonoscopy beginning at 35-40 years of age.— Colonoscopy at age 40, or 10 years before the youngest case in the immediate family, whichever is earlier, than colonoscopy every 5-10 years.

Educational objective: Review side effects of commonly used anticancer drugs.

The important side effects of cisplatin are nephrotoxicity, peripheral neuropathy, ototoxicity and magnesium depletion. Skin pigmentation is an important side effect of bleomycin. Pulmonary fibrosis occurs with busulfan and bleomycin. Cardiomyopathy is a noted side effect of doxorubicin and daunorubicin. Hemorrhagic cystitis occurs with cyclophosphamide.

Educational objective: Review features of graft versus host reaction.

Patients undergoing allogenic bone marrow transplantation receive immunosuppressive medications for 6-12 months post transplantation to prevent allorecognition of the patient by donor T cells. They are at risk for developing chronic graft versus host disease upon withdrawal of immunosuppressive therapy. Manifestations of this syndrome include cataracts, dry red eyes, mouth ulcerations, scleroderma, skin rash, liver function abnormalities typical of biliary tract damage, malabsorption, myositis, pancytopenia and decreased libido.

Educational objective: Review important prognostic factors for large cell lymphoma.

In diffuse large cell lymphoma, patients with performance status 0, 1 are associated with improved survival versus 2-4.

The ECOG score (published by Oken et al in 1982), also called the WHO or Zubrod score (after C. Gordon Zubrod), runs from 0 to 5, with 0 denoting perfect health and 5 death: 0 - Asymptomatic 1 - Symptomatic but completely ambulant 2 - Symptomatic, <50% in bed during the day 3 - Symptomatic, >50% in bed, but not bedbound 4 - Bedbound 5 - Death

Educational objective: Review therapy for hairy cell leukemia.

This patient has the classic findings of hairy cell leukemia, i.e. cytopenias without constitutional symptoms, splenomegaly and hairy cells with cytoplasmic projections (positive TRAP stain). The treatment of choice is 2CDA

For patients with relapsed HCL who have previously been treated with splenectomy, interferon, or 2-deoxyformycin (2'-DCF), retreatment with 2-CDA in the same manner is indicated, especially if they had previously responded to 2-CDA. In patients previously treated with 2-CdA, response rates of 50% are typical. For HCL patients refractory to 2-CDA, or if relapse occurs after 2 cycles of 2-CDA, the authors recommend treatment with 2'-deoxycoformycin (2'DCF, Pentostatin) 4 mg/m2 intravenously every 2 weeks for 3-6 months.

Rituximab is a monoclonal antibody against CD20. In patients with relapsed or refractory HCL, response rates of 50% are reported. Alpha interferon at 2 million U/m2 subcutaneously 3 times a week for 12-18 months can be used to salvage relapsed or refractory HCL patients.

Hypercalcemia is a relatively common complication of malignancy, occurring in approximately 10-20% of cases. The most common malignancies associated with hypercalcemia are breast and lung cancer and multiple myeloma.

Hypercalcemia of malignancy is due to release of calcium from bone by one of three mechanisms--osteolytic metastases, secretion of PTH-related protein, or secretion of calcitriol by tumor. The most common cause of hypercalcemia with nonmetastatic solid tumors is the release of PTH related peptide (humoral hypercalcemia of malignancy). Patients usually have advanced disease and poor prognosis. Of the lung tumors squamuous cell carcinoma has been the most common type of tumor associated with humoral hypercalcemia of malignancy. The small cell lung cancer is associated with many paraneoplastic syndromes (SIADH, Ectopic ACTH etc.), but rarely with hypercalcemia. Other malignancies offered as answers rarely cause paraneoplastic syndromes.

Most bone metastases stimulate bone remodeling in the site of the malignant cell mass and as a result cause increased accumulation of bone-seeking radiopharmaceuticals. This is used to detect bone metastases in a wide variety of malignant neoplastic diseases.

However, some more indolent lesions may result in lesions that are invisible on bone scanning or even producing destruction of bone without any remodeling (cold lesions). These lesions also may be poorly visible on bone scan.

Diseases most commonly producing these invisible bone metastases are multiple myeloma and thyroid cancers. In patients with these diseases, the bone scan should not be used to survey the skeletal system for metastatic disease.

Educational objective: review of characteristic features of multiple myeloma.

This presentation and laboratory findings are suggestive of multiple myeloma. Median age at diagnosis is about 65 years. About two thirds of patients have bone pain at presentation. Pain is most common in the back and chest, and less often in extremities. Pain is usually aggravated by movement and is usually absent during the night except with change in position. Weakness and fatigue are also common symptoms.

Pallor is the most frequent physical finding. Liver is palpable in about 20% and spleen in 5% of patients. Bone metastases are most commonly osteolytic (thought to be mediated by cytokine production) and may result in hypercalcemia (20-30% of patients). Renal failure is common and may be a presenting manifestation of multiple myeloma.

Elevated serum proteins with proteinuria (light chains) are one of the hallmarks of multiple myeloma and may result in amyloidosis. Metastatic disease is unlikely to be associated with either hyperproteinemia or osteoarthritis, which is more widespread and tends to be located in lower lumbar spine. Epidural abscess is usually associated with systemic signs of infection and elevated WBC.

Vertebral compression is common in patients with multiple myeloma but those are caused by the bony destruction by masses of plasma cells rather than osteoporosis.

Educational Objective: Review differences in therapy of rectal versus colonic cancer.

Rectal cancer has a radio-sensitivity not seen in more proximal colon cancer. Pre-operative chemotherapy and radiation therapy can shrink the original lesion and make surgical resection more successful.

Educational Objective: Review improved survival of Dukes C lesions with chemotherapy.

Dukes C lesions with local lymph node involvement have an improved survival following chemotherapy with 5 FU and leucovorin. Colon cancer outside of the rectum is relatively radio resistant.

Educational Objective: Review multiple gene defect principle of metastatic colon cancer.

Colon cancer begins as adenomatous “dysplastic” epithelium and, through multiple genetic defects to this dysplastic tissue, advances through multiple stages from early to late adenoma, carcinoma and metastatic disease.

Educational Objective: Review the Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is an autosomal dominant syndrome with benign hamartomatous polyps from the esophagus to the rectum. It is associated with melanotic spots on the lips, hands, feet, face, perianal, genital, and buccal mucosa. These patients also may have nasal, bronchial, gallbladder, and urinary tract polyps.

Educational Objective: Review the increased risk of extra-intestinal cancers in HNPCC.

Hereditary non-polyposis colorectal cancer carries an increased risk for cancer of the pancreas, ovary, uterus, stomach, and ureter.

Educational Objective: Review Gardner’s Syndrome.

Gardner’s Syndrome is similar to familial adenomatous polyposis except that it is associated with benign extra intestinal growths such as lipomas and ostromas. The colonic polyps start to grow in the second decade of life and uniformly deteriorate into colon cancer by the age of 40. This young man needs a yearly flexible sigmoidoscopy until he shows his first polyps; then he needs a total colectomy.

Educational Objective: Review management of a malignant polyp.

A malignant polyp carries a 5% risk of local lymph node involvement with any of these poor prognostic features: involvement of the margin; poorly differentiated histology; vascular or lymphatic invasion; penetration of the muscularis mucosa. The risk of a partial colectomy is about 2% mortality; therefore this patient should have surgery.

Educational objective: Review features of renal failure associated with multiple myeloma.

Renal failure is not rare in patients with multiple myeloma. This is especially true for those patients having hypercalcemia or those forming excess light chains and therefore developing myeloma kidney, primary amyloidosis, or light chain deposition disease. Renal failure is typically associated with low anion gap (as in the option D of our question). This phenomenon is caused by a large amount of positively charged proteins in the patient’s blood that are not measured.