Exercise-induced dyspnea and cough in a physically fit nonsmoker

Following four months of aggravating symptoms and unexplained weight loss, an anxious patient seeks answers.

Mr. P, 27 years old, presented with stable cough for the past four months. The cough was intermittent and associated with white sputum in the morning (no odor) and dyspnea on exertion. There was no shortness of breath at rest. The symptoms persisted despite treatment for an upper respiratory infection with unknown antibiotics and loratadine (Claritin). The patient described an unintentional weight loss of 5 lb over the past four months. He had been exposed to active TB four years ago. At the time of presentation, results of purified protein derivative testing were negative. He reported no history of smoking or asthma.

Physical exam

Mr. P was afebrile with BP 134/90 mm Hg, pulse 110 beats per minute, temperature 37°C, respiration rate 16 breaths per minute, and room-air pulse oximetry reading 100%. The lower right lobe demonstrated absence of breath sounds, with associated dullness to percussion, decreased tactile fremitus, and positive egophony. There were no wheezes, rhonchi, or rales. Sternal fullness was appreciated on palpation.

The left lung was clear to auscultation. Mr. P had a liver span of 12 cm in the right midclavicular line and a palpable spleen. He also had painless, firm, mobile inguinal adenopathy. At this point, the differential diagnosis included pneumonia, lung cancer, bronchitis, and TB.

Further investigation

A complete blood count with differential was within normal limits. Results of a basic metabolic panel and liver enzyme panel were also normal. Blood cultures showed no growth after five days. An enzyme-linked immunosorbent assay for HIV was negative. Sputum culture and stain were both negative.

Chest x-ray showed right lower-lobe fluid and a superior anterior mediastinal mass. The mass was confirmed by CT of the chest showing a 14.7-cm × 8.3-cm growth with associated enlarged paratracheal lymph nodes. The differential now included thymoma, lymphoma, teratoma, and thyroid mass.

Diagnosis

In Mr. P’s case, lymphoma—specifically Hodgkin’s lymphoma—was the correct diagnosis. In Hogkin’s, both plain films and CT will demonstrate anterior mediastinal and paratracheal nodes as the most frequently involved groups.1 In most cases, the lymphadenopathy is bilateral but asymmetrical. The findings of paratracheal nodes on the patient’s CT demanded further investigation. Mr. P underwent thoracentesis, which demonstrated yellow, hazy fluid.

Interventional radiology fine-needle aspiration showed lymphoid cells with fibrous and adipose tissue. Lymphoid cells were a mixture of B and T cells. Video-assisted thoracic surgery biopsy demonstrated Reed-Sternberg cells. Signs and symptoms of Hodgkin’s lymphoma include fever (>38°C), night sweats (drenching and recurrent), weight loss (significant only if at least 10% of body weight in past six months), pruritus, persistent fatigue, painless swelling of lymph nodes, pain of involved regions after alcohol intake, splenomegaly (30%), and hepatomegaly (5%).2,3

Hodgkin’s disease is a malignant lymphoma with distinct histology, biologic behavior, and clinical characteristics. It has a bimodal presentation with the greatest peak in the third decade of life and a second, smaller peak after age 50. It is slightly more common in men and less common in African Americans. Studies suggest a small increase in incidence of Hodgkin’s disease in patients with a history of infectious mononucleosis.2

Definitive diagnosis is with biopsy portraying a histologically unique picture comprising 1%-2% neoplastic Reed- Sternberg cells against a background of a variety of reactive mixed inflammatory cells.2 Staging is based on the Cotswold staging classification:

Stage I: single lymph-node region or lymphoid structure (e.g., spleen, thymus, Waldeyer’s ring)
Stage II: two or more lymph-node regions on the same side of the diaphragm (i.e., the mediastinum is a single site, hilar lymph nodes are lateralized)
Stage III: lymph-node regions or structures on both sides of the diaphragm:
III1: with or without involvement of splenic, hilar, celiac, or portal nodes
III2: with involvement of para-aortic, iliac, or mesenteric nodes
Stage IV: extranodal sites

Discussion

Thymoma is the most common primary anterior mediastinal tumor (20%) in adults.2 Patients are usually asymptomatic but can present with myasthenia gravis-related symptoms, substernal pain, dyspnea, or cough. Biopsy reveals tonofibrils, which can differentiate thymoma from other tumors.

Teratomas, which comprise 10% of anterior mediastinal masses,1 are found at all ages, particularly in adolescents and young adults. They are usually asymptomatic and diagnosed incidentally on chest radiography or CT. However, they may give rise to cough, dyspnea, or chest pain if they compress the bronchial tree or superior vena cava or if they rupture into the mediastinum or lung.4 Fat, which may be identified within the mass on the plain film, leads to a more specific diagnosis.

Thyroid masses almost always displace the trachea. Additional diagnostic clues that a mass represents or is associated with the thyroid gland include identifying its paratracheal position, palpating its intimacy with identifiable thyroid tissue, and observing its vertical motion with swallowing.1,2

Treatment

Treatment for early stage Hodgkin’s lymphoma (stage I or II) combines low-dose radiation therapy to clinically involved sites with chemotherapy using doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD). Treatment for stage III or IV is combination chemotherapy; ABVD four to six cycles with the recommendation to continue treatment for at least two cycles beyond a complete clinical remission.2 Mr. P was referred to oncology with plans for combined radiation and chemotherapy. His prognosis was good.

Ms. Sciacchetano is a recent graduate of the University of Medicine & Dentistry of New Jersey (UMDNJ) physician assistant program, in Piscataway. Ms. O’Connell is associate professor in the UMDNJ PA program and a contributing editor to The Clinical Advisor.

References

1. Grainger RG, Allison DJ, Dixon AK. Grainger & Allison’s Diagnostic Radiology: A Textbook of Medical Imaging. 4th ed. Philadelphia, Pa.: Churchill Livingstone; 2001: chap 17.

2. Goldman L, Ausiello D. Cecil Textbook of Medicine. St. Louis, Mo.: Elsevier Health Sciences; 2004: chap 194.

3. Noble J. Textbook of Primary Care Medicine. 3rd ed. St. Louis, Mo.: Mosby; 2001: chap 182.

4. Emedicine. Teratoma, cyctic. Available at www.emedicine.com/med. Accessed August 15, 2007.

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