A 66-year-old postmenopausal woman presents with a painless breast mass and is found to have a 3-cm infiltrating ductal breast cancer. Sentinel node sampling reveals metastatic cancer in the sentinel node; a formal axillary node dissection shows that 4 of 13 nodes are involved by the malignant process. Both estrogen and progesterone receptor are expressed in the tumor. There is no evidence of metastatic disease outside the axilla. In addition to lumpectomy and radiation therapy to the breast and axilla,
what should her treatment include next?
This woman is at high risk of recurrent breast cancer, an ultimately fatal event. Adjuvant therapy has been shown to decrease the chance of recurrence by 40%. This translates into a proven survival advantage for the woman; the advantages of treatment far outweigh the risk of side effects. Therefore, no therapy or only local therapy (eg, radiation therapy) would represent inadequate treatment.Postmenopausal women who are ER or PR positive are generally treated with adjuvant hormonal therapy. Premenopausal women, or women whose tumor does not contain ER or PR, will usually need adjuvant chemotherapy. Both tamoxifen (an estrogen receptor antagonist) and aromatase inhibitors (eg, letrozole, anastrozole) are effective in decreasing the rate of recurrence. Although aromatase inhibitors may be slightly more effective than tamoxifen, they are much more expensive, can produce troublesome side effects, and unlike tamoxifen do not improve bone density. This choice is often based on the preference of the patient and her oncologist. In a woman 5 or more years after menopause, the ovaries produce inconsequential amount of estrogens. Therefore oophorectomy, sometimes used in the premenopausal woman, is an inappropriate choice for this patient.
A 64-year-old African American man presents for evaluation of a painless “lump” in the left thigh. He first noticed the abnormality about 1 month previously and thinks it has increased in size; there is no prior history of trauma. On examination, you find a 5-cm soft tissue mass, firm to hard in consistency, in the soft tissue above the knee. There is no tenderness or erythema; the mass is deep to the subcutaneous tissue and appears fixed to the underlying musculature. Inguinal lymph nodes are normal.
Which of the following is the most appropriate management of this patient?
Although lipomas are the commonest soft tissue mass, they are soft, move with the subcutaneous tissue, and grow very slowly. Any atypical or enlarging soft tissue mass should be further evaluated, either by CT or MRI scan or by biopsy, because this is how soft tissue sarcomas present. Bone scan is usually normal. The size, firmness, and fixity to deep tissues are all worrisome features in this patient. An abscess would be soft and fluctuant, and hematomas are painful and associated with trauma. Therefore a biopsy should be requested even if the CT scan is reassuring. An open biopsy would be the preferred approach. Sixty percent of soft tissue sarcomas arise in the extremities, with the lower extremities three times as common as the upper extremities. Several histological types are possible and are not predictable from clinical features; malignant fibrous histiocytomas are most common. The only curative approach is complete surgical resection. Radiation and chemotherapy have a role in adjuvant or palliative therapy. Occasional patients with favorable metastatic disease enter long-term remission with aggressive therapy. Soft tissue sarcomas metastasize hematogenously, most often to the lungs; lymph node metastases would not be expected.
A 47-year-old woman complains of fatigue, weight loss, and itching after taking a hot shower. Physical examination shows plethoric facies and an enlarged spleen, which descends 6 cm below the left costal margin. Her white cell count is 17,000 with a normal differential, the platelet count is 560,000, and hemoglobin is 18.7. Liver enzymes and electrolytes are normal; the serum uric acid level is mildly elevated.
What is the most likely underlying process?
This patient has polycythemia vera, a clonal proliferative disorder of the bone marrow in which all three cell lines (red blood cells, platelets, and myelocytes) are overproduced. The other classic myeloproliferative disorders are chronic myelogenous leukemia, essential thrombocytosis, and myelofibrosis. It is important to distinguish myeloproliferative syndromes (where one or more cell lines proliferate) from myelodysplastic syndromes (where one or more cell lines—usually red cells—are deficient). In myelodysplastic disorders, white blood cells and platelets are normal, at least initially. These patients present with anemia, often in association with mild macrocytosis and other features of altered marrow maturation (ringed sideroblasts, hypolobulated polys, etc). Splenomegaly and cellular overproduction are not features of the myelodysplastic syndromes. Cushing syndrome can cause facial plethora but would not account for the splenomegaly or hematological changes. Gaisböck syndrome causes erythrocytosis with a normal red cell mass (resulting from diminished plasma volume) but does not cause splenomegaly, leukocytosis, or thrombocytosis. Polycythemia vera does not occur as part of a paraneoplastic process.
A 20-year-old black man presents to the emergency room complaining of diffuse bone pain and requesting narcotics for his sickle cell crisis.
Which of the following physical examination features would suggest an alternative diagnosis to sickle cell anemia (hemoglobin SS)?
Splenomegaly is not typical of sickle cell anemia. Recurrent splenic infarcts usually occur during childhood and lead to a small, infarcted spleen with functional asplenia. These patients often have Howell-Jolly bodies on peripheral blood smear (indicative of asplenia) and have an increased incidence of infection with encapsulated organisms. The presence of an enlarged spleen in a patient with sickled cells on peripheral blood smear is most often seen in hemoglobin SC disease. Any hemolytic anemia can result in an unconjugated hyperbilirubinemia and low-grade icterus. Anemia results in a hyperdynamic circulation and a systolic ejection murmur. Ankle ulcers and other chronic skin ulcers may be persistent problems in patients with SS disease, particularly in those with severe anemia. Patients with sickle cell crisis often present with leukocytosis, related both to stress and to the asplenia.
A 30-year-old black man plans a trip to India and is advised to take prophylaxis for malaria. Three days after beginning treatment, he develops pallor, fatigue, and jaundice. Hematocrit is 30% (it had been 43%) and reticulocyte count is 7%. He stops taking the medication.
The next step in treatment should consist of which of the following?
This patient has developed a hemolytic anemia secondary to an antimalarial drug. Toxins or drugs such as primaquine, sulfamethoxazole, and nitrofurantoin cause hemolysis in patients with G6PD deficiency, which occurs most commonly in African Americans. Since the G6PD gene is carried on the X chromosome, most affected patients are males. The drugs that cause hemolysis in G6PD deficiency are oxidizing agents. Oxidant stress on red blood cells is normally counteracted by reduced glutathione. NADPH (which is required to regenerate reduced glutathione after it has been oxidized) is produced by the hexose monophosphate shunt. G6PD is the first enzyme in this metabolic pathway. If this enzyme is less active, the cell cannot replace reduced glutathione and succumbs to oxidizing stress. Clinically this can range from mild to life-threatening hemolysis. In mild cases, no treatment is necessary; once the offending drug is eliminated, the hemolysis resolves.
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