Abbasi J. Akhtar, MD, MRCP Professor Department of Medicine Giovinetza Hasbun, MD Resident Department of Family Medicine Rose Liu, MD Resident Department of Radiology Hilary Nwosu, MD Resident Department of Medicine Thienkhai H. Vu, MD, PhD Resident Department of Radiology Naziuh Bishay, MD Resident Department of Family Medicine Ram K. Chillar, MD Associate Professor Department of Medicine Division of Hematology-Oncology Charles R. Drew University of Medicine and Science Los Angeles, Calif Case Presentation

A 19-year-old Hispanic woman was transferred from a community hospital to our institution with a diagnosis of pneumonia. Her history included a 1-week duration of progressive nonproductive cough, which was still present at the time of admission, and increasing shortness of breath accompanied by pleuritic chest pain that had started 3 days before admission. Two weeks earlier she had a painful lump drained in the perineal area; the presumptive diagnosis was ischiorectal abscess. No pus was evident, and no biopsy was done at that time; rigid sigmoid­oscopy findings were normal. The patient denied any history of fever, chills, night sweats, diarrhea, or rectal or vaginal bleeding or discharge. She also denied smoking, taking oral contraceptives, or any substance abuse.

Physical examination revealed: pulse, 114 beats/min; blood pressure and temperature, normal. She was alert, oriented, and had no peripheral adenopathy. Pulmonary auscultation revealed scattered rhonchi. Cardiac auscultation and abdominal examination were normal. A 2 x 2-cm ulcer with granulation tissue was seen in the left perineal area, and a 4 x 2-cm nontender mass was found along the posterior fourchette.

Initial laboratory tests showed: hemoglobin, 14.9 g/dL; total white blood cell count, 11.1 x 109/L (normal differential); platelet count, 364 x 109/L. Arterial blood gases were normal on room air.

During the hospital stay, her shortness of breath progressed; her Pao2 was 53 mm Hg. Chest x-ray revealed left hilar adenopathy and diffuse, patchy, and focal opacities of varying sizes bilaterally (Figure 1). The patient was placed in respiratory isolation. Three sputum tests were negative for Mycobacterium tuberculosis but positive for yeast. A tuberculin skin test was negative, as was an HIV test. Computed tomography (CT) scan showed multiple bilateral diffuse lung nodules, ranging in size from 0.5 to 2 cm (Figure 2). Open wedge biopsy of the lung was performed. Medications prescribed at the hospital included levo­floxacin (Levaquin), fluconazole (Diflucan), clindamycin (Cleocin), and trimethoprim/sulfamethoxazole (Bactrim, Septra).

The biopsy revealed a malignant, small, round blue-cell tumor in a nested pattern suggestive of rhabdo­myosarcoma. Subsequent immunopathologic studies confirmed the diagnosis of the alveolar subtype of rhabdomyosarcoma. Increasing respiratory distress led to respiratory failure, requiring ventilatory support. CT scan of the abdomen demonstrated a 9.4 x 9.6-cm heterogeneous mass in the pelvic floor (Figure 3). Bone scan suggested metastasis to the fifth lumbar vertebra, pubic symphysis, right shoulder, and right seventh rib.

The hematology/oncology service was consulted and chemotherapy started. Each 4-day cycle of chemotherapy was to be repeated for 4 weeks, for a total of 7 cycles. Her response to initial chemotherapy was dramatic. She gained strength and weight, and improvement in her overall clinical well-being was evident, despite a few episodes of febrile neutropenia, thrombocytopenia, dysphagia, and upper gastrointestinal (GI) bleeding during the course of chemotherapy. Upper GI endoscopy showed esophageal erosions, with whitish plaques suggestive of esophageal candidiasis and antral gastritis.

Histopathology and immunopathology of the esophageal biopsy specimens confirmed the presence of Candida albicans and herpes simplex virus. Treatment with fluconazole was continued, and famotidine (Pepcid), acyclovir (Zovirax), sucralfate (Carafate), ceftazidime (eg, Fortaz, Ceptaz), tobramycin, and filgrastim (Neupogen) were added to the treatment regi­men. The patient improved significantly, and her cough and shortness of breath subsided.

A needle biopsy of the healing ischiorectal ulcer revealed tissue that was histologically similar to that obtained in the open lung biopsy, suggesting this lesion may have been a primary site of the rhabdomyosarcoma.

The patient was discharged home after 22 days and was readmitted 1 week later for the second course of chemotherapy, which was given uneventfully. At this time, the patient was feeling much better. A follow-up chest radiograph and CT scan of her chest and pelvis 1 month later showed resolution of the pulmonary nodules and pelvic mass.

Discussion
Rhabdomyosarcoma is a highly malignant soft-tissue sarcoma. It is the most common soft-tissue sarcoma in children, accounting for about 50% of these lesions in children in the United States.¹ Rhabdomyosarcoma originates from primitive mesenchymal cells, which normally form skeletal muscle, but it can occur in sites without striated muscles, such as the urinary bladder. Rhabdomyosarcoma occurs in 3 forms: pleomorphic, predominantly affecting the extremities of adults; alveolar, affecting muscles of the extremities, trunk, and orbital region mainly in adolescents and young adults; and embryonal, affecting the head, neck, lower genitourinary tract, pelvis, and extremities predominantly in infants and children. Signs and symptoms depend on the tumor site. The thorax, including the lungs and diaphragm, may be a primary or metastatic site of rhabdomyosarcoma.^2,3 Presenting symptoms, such as bone pain and neurologic complaints, can occur secondary to distant metastases from an undetermined primary neoplasm.^4,5 Unusual presentations of rhabdomyosarcoma include hematologic malignancy, such as leukemia.^6,7

Although rhabdomyosarcoma is a common tumor in children and adolescents, primary sarcomas of the thorax are rare. Other primary intrathoracic sarcomas include angiosarcoma, leiomyosarcoma, and sarcomatoid variant of mesothelioma. They may arise from the lung, mediastinum, pleura, or thoracic wall. Presenting symptoms usually depend on the location of the tumor. Thoracic wall tumors may present as a painful swelling, whereas pulmonary neoplasms may present as a solitary mass, a diffuse reticular pattern simulating pneumonia, or as multiple pulmonary nodules, as in our patient. The most likely explanation for our patient’s painful swelling in the perineal area for 4 months is that the pulmonary lesions were metastatic rather than primary. The treating physicians considered the possibility of Crohn’s disease and performed a sigmoidoscopy. The possibility of rhabdomyosarcoma, however, was not considered at that time, and no biopsies were done.

Rhabdomyosarcoma is known to occur in the perineal region, and tumors at this site may mimic abscesses, as was the case in our patient.⁸ A timely biopsy would have revealed the diagnosis earlier and could have possibly facilitated an improved prognosis.⁹

Rhabdomyosarcoma is thought to arise from primitive mesenchymal cells and can present in a variety of organs and tissues. The common sites for rhabdomyosarcoma are, in order of frequency, head and neck, genitourinary, and extremities. The bladder and prostate are the common genitourinary sites.

Definitive diagnosis depends on a generous biopsy of the tumor and histology. The diagnosis of rhabdomyosarcoma may be relatively easy to make and straightforward, or challenging and requiring immunohistochemical, electron microscopic, and molecular genetic studies to differentiate it from extraosseous Ewing’s sarcoma or primitive neuroectodermal tumors of soft tissue.¹⁰

CT scans, technetium Tc 99m-diphosphonate scans, and bone marrow aspiration and biopsy are helpful in the diagnosis and metastatic work-up. Magnetic resonance imaging has been shown to be particularly helpful for diagnosis and follow-up of genitourinary, pelvic, or perineal rhabdomyosarcoma.¹¹ Examination of cerebrospinal fluid may be necessary if meningeal involvement is suspected. Pretreatment staging based on surgical pathology or the tumor–node–metastasis system may help in choosing the approach to treatment as well as evaluating treatment and comparing the outcome of different treatment regimens. Timely therapy for this type of tumor may result in cure rates exceeding 70%.⁹

Patients with no detectable metastatic disease have a far better prognosis than those with widespread disease.⁹ Our patient had widespread disease.

Complete surgical resection of localized disease may result in cure. Wide-field radiation is indicated if residual disease is evident after maximum possible surgical resection of all involved tissue. Brachytherapy (direct application of radionuclide to the tumor site) may be used in some cases of minimal residual disease, especially if extended radiation therapy to all involved areas is not feasible. Its advantages include delivery of high-dose radiation locally to the involved areas, while sparing adjacent normal tissues.¹² Intensive chemotherapy has been shown to result in complete or partial responses.¹³ Commonly used chemotherapeutic agents include vincristine, cyclophosphamide, ifosfamide, melphalan, doxorubicin, actinomycin D, cisplatin, and etoposide in various combinations.

Recurrence is associated with poor prognosis. A recent study showed an overall 5-year survival rate of about 28% in patients with recurrent rhabdomyosarcoma, although those with fewer risk factors (ie, alveolar subtype, parameningeal or other primary sites, systemic recurrence, and recurrence with therapy) had higher survival rates.¹⁴

A high index of suspicion and prompt biopsy are recommended for mass lesions in children and young adults, especially when these lesions arise de novo in the perineal area.¹⁵ An aggressive neoplasm should be suspected when pneumonia and respiratory failure occur in a young, immunocompetent patient. Pulmonary nodules should be evaluated to exclude malignancy.

Conclusion
Although rhabdomyosarcoma may metastasize to the lungs and patients may develop eventual respiratory failure, we could not find cases of rhabdomyosarcoma presenting as respiratory failure. Our 19-year-old Hispanic patient was admitted with a diagnosis of pneumonia, developed respiratory failure, and required ventilatory support. Her subsequent hospital course was notable for suspicion of pulmonary masses, lung biopsy, diagnosis of rhabdomyosarcoma, and induction chemotherapy. The patient responded favorably to initial and follow-up chemotherapy.

References
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