Young Man With Cough and Dyspnea

A 22-year-old man presents to theemergency department with a2-week history of a worsening nonproductive,irritating dry cough andexertional dyspnea. The patient hasbeen otherwise healthy. He deniesfever, rigors, night sweats, hemoptysis,chest pain, palpitations, orthopnea,paroxysmal nocturnal dyspnea,ankle edema, and lymphadenopathy.History. The patient has lostabout 30 lb in the last 3 months. Hehas had no sick contacts, is not sexuallyactive, and does not smoke oruse illicit drugs. There is no historyof recent travel.Examination. This moderatelywell-built and well-nourished youngman is not in acute distress; hecoughs intermittently. Temperatureis 37.2C (99F); heart rate, 120beats per minute and regular; respiration rate, 24breaths per minute; blood pressure (right upper limb),130/88 mm Hg; weight, 120 lb; height, 66 in. There isno evidence of adenopathy, clubbing, cyanosis, or ankleedema. Chest examination reveals poor movement ofthe left chest with impaired note on percussion on theleft side; trachea is deviated to the right side. Breathsounds are absent over the entire left lung field. Jugularvein pulse is normal. Heart sounds are normal with nomurmur or gallop. Abdominal examination reveals noorganomegaly or tenderness. Neurologic examination isnormal.Laboratory studies. White blood cell count,5600/L, with 68% polymorphonuclear leukocytes, 24%lymphocytes, 4% monocytes, and 4% eosinophils; hemoglobin,11.8 g/dL; platelet count, 186,000/L; erythrocytesedimentation rate, 90 mm/h. Urinalysis reveals nored blood cells or casts. Serum sodium, 138 mEq/L;potassium, 4 mEq/L. Blood urea nitrogen level, 26mg/dL; serum creatinine, 1 mg/dL; albumin, 3.2 g/dL.Total bilirubin, 1 mg/dL; aspartate aminotransferase,26 IU/L; alanine aminotransferase, 22 IU/L. Alkalinephosphatase, 116 IU/L; lactate dehydrogenase, 825 IU/L;HIV test is negative.An ECG reveals sinus tachycardia. The chest filmis shown here.In view of the clinical, laboratory, and radiographicfindings, which of the following is the mostappropriate next step? A. Emergent echocardiogram
B. Bronchoscopy
C. Careful examination of the testicles
D. Sputum examination for acid-fast bacilli
E. Rectal examination with stool test for occult blood
WHAT'S WRONG:The chest radiograph shows alarge mass in the left lung thatshifts the cardiac silhouette andmediastinum to the right. The findingof a dense lung infiltrate in ayoung man mandates a careful examinationof the testicles, C.Testicular cancers are common inthis age group, and they metastasizerapidly to the lung.Although the patient did notvoluntarily provide a relevant history,the brother who accompaniedhim mentioned having been toldby the patient that his right testiclehad been enlarging during the past3 months (Figure 1). Examinationconfirms a large, firm mass in theright testis.Hospital course. Ultrasonographyreveals that the mass measures9.2 x 9.8 x 7.7 cm and is locatedin the upper anterior part ofthe testicle. α-Fetoprotein level is14,073 ng/mL; human chorionicgonadotropin (hCG) level is 23IU/mL (normal, less than 5 U/mL).A chest CT shows a solid mass inthe left lung (Figure 2). A fine-needle aspiration of the mass demonstratesembryonal nonseminomatousgerm cell carcinoma.A brain CT shows a 7-cm massand surrounding edema in the frontallobe (Figure 3). An abdominalCT shows a 5.7 x 6.3 x 5.5-cmmass in the spleen. Results of a lungbiopsy reveal metastatic disease.Based on the results of these studies,the disease is classified as stageIII.The patient undergoes radicalinguinal orchiectomy, and chemotherapy(cisplatin, vinblastine, andbleomycin) and radiation therapyare started. He will be followed upregularly in the oncology clinic.¹TESTICULAR CANCER:
OVERVIEW AND EPIDEMIOLOGY
Testicular cancer is the most common solid malignancyin men; it accounts for 1% of all cancers in men.Malignant testicular tumors, which comprise 95% ofcancers that develop in the testis, arise from primordialgerm cells. Germ cell tumor is the most common solidtumor in men between the ages of 15 and 34 years. Approximately7000 new cases are reported in the UnitedStates annually. The highest incidence is found in theScandinavian countries, Germany, and New Zealand; thelowest is in Asia and Africa.Germ cell tumors occur 5 times more frequently inwhite than in black men. Familial clusters have been reported,particularly among siblings. Predisposing factorsfor testicular germ cell tumors include cryptorchidismand Klinefelter syndrome. These tumors are alsomore likely to occur in patients with HIV infection.HISTOLOGIC CLASSIFICATION
Malignant testicular tumors include seminomasand nonseminomatous tumors, embryonal carcinoma,teratomas, choriocarcinoma, and yolk sac carcinomacell types. Embryonal carcinoma is the most undifferentiatedcell type and may produce elevated serum concentrationof α-fetoprotein, hCG, or both.CLINICAL MANIFESTATIONS
Patients with germ cell tumors present initially withreports of a mass or, less frequently, with signs andsymptoms of metastasis, in which case examination ofthe testicles becomes critical. These signs and symptomsinclude:

• Neck mass (supraclavicular lymph node metastasis).
• Cough or dyspnea (pulmonary metastasis).
• Anorexia, nausea, vomiting, or GI hemorrhage (retroduodenalmetastasis).
• Lumbar pain (bulky retroperitoneal disease involvingthe psoas muscle or nerve roots).
• Bone pain (skeletal metastasis).
• Seizures, paresthesias, weakness, bladder or boweldysfunction (central or peripheral nervous system--cerebral, spinal cord, or peripheral root involvement).
• Unilateral or bilateral lower extremity swelling (iliac orcaval venous obstruction).

A painless testicular mass is considered virtuallypathognomonic of a primary testicular tumor, but it occursin only a small number of patients. More commonly,patients complain of diffuse testicular pain, swelling,firmness, or a combination of these findings.Because infectious epididymitis is more commonthan tumor, an initial trial of antibiotic therapy is often undertaken. If testicular pain and other symptoms donot improve within 2 to 6 weeks, testicular ultrasonographyis warranted. If a testicular tumor is present, theimage usually shows single or multiple intratesticularhypoechoic masses or diffuse abnormalities with microcalcifications.Bilateral tumors are rare. In 2% of patients,a second primary tumor develops in the contralateraltestis. Gynecomastia is seen in 5% of men withgerm cell tumor.A radical inguinal orchiectomy with ligation of thespermatic cord at the inguinal ring is the recommendedtreatment for all patients with testicular tumor. Histologicevaluation identifies the specific tumor type.

SERUM TUMOR MARKERS

α-Fetoprotein levels are elevated in 40% to 60% ofpatients with metastases. They may also be elevated inpatients with liver damage secondary to infection ordrug or alcohol use; hepatocellular carcinoma; andother GI cancers.Increased serum concentrations of hCG are observedin 15% to 20% of patients with seminomas and40% to 60% of those with metastatic nonseminomatoustumors. An elevated level of lactate dehydrogenase is anonspecific marker found in 60% of patients with nonseminomatoustumors and in 80% of those who haveseminomas.The concentrations of tumor markers should decreaseafter surgery and chemotherapy. Persistence ofelevated levels indicates active residual disease.

PATTERN OF METASTASIS

Germ cell tumors are rapidly growing neoplasms;60% to 70% have metastasized by the time of diagnosis.The first site of metastasis, via the lymphatic channels,is the retroperitoneal lymph nodes, below the renalvessels.The lungs are almost always the first site ofhematogenous spread. Left supraclavicular adenopathyand pulmonary nodules occur with or without retroperitonealdisease. The liver, bone, or brain is rarely thesole site of metastasis.In 40% of patients, the tumor is limited to the testis;40% have retroperitoneal involvement and the remaining20% have supradiaphragmatic involvement or visceralorgan spread.

RADIOGRAPHIC EVALUATIONS

Required imaging studies include chest radiographyand CT of the abdomen and pelvis. A CT scan ofthe chest is ordered if mediastinal, hilar, or lungparenchymal disease is suspected. CT or MRI of thebrain is performed in patients with neurologic signs andsymptoms.

CLASSIFICATION OF DISEASE STAGES

Germ cell tumors are classified as follows:

• Stage I: Disease is limited to the testis, epididymis, orspermatic cord.
• Stage II: Disease is limited to the retroperitoneallymph nodes.
• Stage IIA: Nodes are smaller than 2 cm.
• Stage IIB: Nodes are between 2 and 5 cm.
• Stage IIC: Nodes are larger than 5 cm.
• Stage III: Disease is metastatic to supradiaphragmaticnodal or visceral sites.

TREATMENT

After radical inguinal orchiectomy, patients withstages I, IIA, or IIB disease are treated with radiation. Inadvanced disease, a chemotherapeutic regimen of cisplatin,vinblastine, and bleomycin or cisplatin with etoposideis initiated.

PROGNOSIS

With combined surgery and chemotherapy, the5-year survival rate is about 90% in patients who haveseminomas or nonseminomatous tumors without metastases.In patients with stage III disease, the cure rate is20% to 25%.

References:

FOR MORE INFORMATION:

• Bosl GJ, Motzer RJ. Testicular germ cell cancer. N Engl J Med. 1997;337:242-253.
• Einhorn LH. Treatment of testicular cancer: a new and improved model.J Clin Oncol. 1990:8:1777-1784.
• Jerome P, Richie JP, Steele GS. Neoplasms of the testis. In Walsh PC, RetikAB, Vaughan ED Jr, et al, eds. Campbell’s Urology. 8th ed. New York: Elsevier;2002.