Journal of Bronchology & Interventional Pulmonology:
The Use of CP-EBUS-TBNA in the Diagnosis of Chondrosarcoma in a Patient With Maffucci Syndrome
Wang, Ruobing MD*,†; Folch, Erik MD, MSc*; Paul, Manju MD*; Maskey, Ashish MD*; Allard, Felicia MD‡; Majid, Adnan MD, FCCP*
*Department of Surgery, Beth Israel Deaconess Medical Center, Division of Thoracic Surgery and Interventional Pulmonology, Harvard Medical School
†Department of Pediatrics, Division of Respiratory Diseases, Boston Children’s Hospital, Harvard Medical School
‡Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Disclosure: There is no conflict of interest or other disclosures.
Reprints: Adnan Majid, MD, FCCP, Beth Israel Deaconess Medical Center, 185 Pilgrim Road, Deaconess 201, Boston, Ma 02215 (e-mail: firstname.lastname@example.org).
Received June 6, 2013
Accepted March 5, 2014
We report a case of a 52-year-old white woman with Maffucci syndrome, a rare skeletal disorder characterized by multiple cartilage-forming tumors (enchondromas). She was referred for evaluation of an enlarging pulmonary nodule. Her positron emission tomography-computed tomography scan revealed a low-density, tubular lesion in the superior segment of the left lower lobe of the lung. She underwent a convex-probe endobronchial ultrasound (CP-EBUS)-guided transbronchial needle aspiration (TBNA) that confirmed metastatic chondrosarcoma. Although CP-EBUS-TBNA has become an established tool for diagnosing and staging of non–small cell lung cancer, analysis of samples from rare tumors such as sarcomas by cytology alone is often inadequate and histologic confirmation using more invasive procedures is often required. Interestingly in our case, the diagnosis of chondrosarcoma was established from the cytology specimen obtained with a 21-G needle without the need for further tissue sampling. Moreover, the location of the lesion was the superior segment of the left lower lobe, an area typically not accessible by CP-EBUS, due to the size of the airway. Considering together, the successful diagnosis of a rare tumor such as sarcomas by CP-EBUS-TBNA modality indicates the growing importance of this minimally invasive technology.
Maffucci syndrome is a rare genetic disorder caused by somatic mosaic mutations in the isocitrate dehydrogenase (IDH)1 and IDH2 genes, characterized by cartilage-forming tumors (enchondromas), bone deformities, and hemangiomas.1 These enchondromas can become malignant in as many as one third of the cases. Malignant transformation usually occurs over 40 years or more, and results in chondrosarcomas or vascular neoplasms. Maffucci is a rare syndrome with <100 cases reported in the English literature and only 3 in the bronchoscopy arena.2–4 We report a case of a 52-year-old white woman with Maffucci syndrome who presented with a pulmonary nodule. We established the diagnosis of chondrosarcoma from the cytology specimen obtained with a 21-G needle under convex-probe endobronchial ultrasound (CP-EBUS) guidance.
A 52-year-old white woman with Maffucci syndrome was referred for the evaluation of an enlarging pulmonary nodule. She was a former smoker of 20 pack-years. Twelve years earlier, she was diagnosed with chondrosarcoma of the left humerus for which she underwent resection and prosthetic reconstruction. Four months before the presentation, she was diagnosed with the recurrence of chondrosarcoma involving her right distal femur and left pelvis. At that time, an integrated positron emission tomography-computed tomography scan revealed a low-density, tubular lesion involving the superior segment of the left lower lobe of the lung (Figs. 1A, B). Aside from limitation of mobility due to pain in the right femur, the rest of the physical examination was unremarkable. Given her past medical history, the differential diagnosis for the solitary lung nodule included: pulmonary metastatic chondrosarcoma, hemangioma, lymphangioma, and primary lung cancer. She was scheduled for a flexible bronchoscopy and a CP-EBUS to characterize the lesion (cystic, solid, vascular) and obtain diagnostic tissue by using a 21-G transbronchial needle aspiration (TBNA).
Flexible bronchoscopy under general anesthesia demonstrated a normal airway except for hypervascularity in the distal left main stem bronchus. Next, the CP-EBUS bronchoscope was introduced and the target lesion was easily identified with ultrasonography that appeared to be solid. Doppler flow showed that the lesion was nonvascular (Figs. 2A, B). Diagnostic tissue obtained by the TBNA under real-time ultrasound guidance demonstrated single and sheets of epithelioid cells with smooth nuclear borders and small prominent nucleoli. Multinucleated forms were also seen. These cells were surrounded by abundant myxomatous chondroid matrix (Fig. 3). These findings were consistent with metastatic chondrosarcoma and were similar to the features seen on the patient’s prior femoral resection and biopsies.
We present here the successful use of cytology specimens obtained from CP-EBUS-TBNA in the diagnosis of pulmonary metastatic chondrosarcoma in a patient with Maffucci syndrome. Maffucci syndrome is a rare, nonhereditary mesodermal dysplasia usually associated with mutations in the IDH1 or IDH2.1 The manifestations occur mostly in childhood and early puberty, with the appearance of benign enchondromas with asymmetric distribution in the phalanges and long bones, as well as diffuse hemangiomas.5 The unilateral distribution of enchondromas is usually known as “Ollier disease.”4
Malignant transformation of endrochondromas into chondrosarcoma can occur and affects 17% to 30% of the patients.6–8 Vascular neoplasms such as hemangiosarcomas and lymphangiosarcomas have also been described.6,9 In our patient who presented with a pulmonary nodule, it was necessary to differentiate between pulmonary metastatic chondrosarcoma, primary lung tumor, benign inflammatory process, and lymphatic lesion, due to the different therapeutic and prognostic implications. Despite scant data on pulmonary resection of the metastatic chondrosarcomas, studies on pulmonary metastasectomy have proven survival benefit in patients with sarcomas.10 Thoracic chondrosarcoma usually occur as metastases from a distant site, and very rarely as a primary pulmonary chondrosarcoma.11 In contrast, if this were primary lung cancer she would likely require an anatomic resection. Pulmonary lymphangiomas are extremely rare, with only a few case reports in the literature. Although it is considered a benign vascular malformation, surgical resection is still recommended by some due partly to the development of respiratory symptoms, and partly to the unclear risk for malignant transformation.12 Others have also proposed close observation if the tumor does not cause symptoms and compression of vital structures.13
CP-EBUS-TBNA has become an established tool for diagnosing and staging non–small cell lung cancer, with a sensitivity and specificity reported to be up to 93% and 100%, respectively.14,15 Recently, this minimally invasive modality has been increasingly used for the sampling of pulmonary and mediastinal masses in both malignant and benign diseases, as well as extrathoracic malignancies, where CP-EBUS-TBNA had a sensitivity of 85% to detect pulmonary metastasis and prevented invasive surgical procedures in 61%.16 Most cases of extrathoracic malignancy were carcinomas of the head and neck, colon, breast, kidney, prostate, esophagus, thyroid, and melanomas.17,18 Analysis of samples from rare tumors such as sarcomas by CP-EBUS-TBNA was thought to be more challenging as cytology may be inadequate and histologic confirmation is often required. The successful diagnosis of a case of spinal chondrosarcoma in a patient with hereditary multiple exostoses by CP-EBUS-TBNA has been reported previously.2 In that particular case, cytological studies revealed atypical cells with nuclear body on Papanicolaou stain; it was the tissue sample obtained by CP-EBUS-TBNA showing tumor cells positive for Ki67 antibody that confirmed the diagnosis of chondrosarcoma. This was also the first report of attempting genetic studies on the obtained samples, but the mutation of EXT1 gene of hereditary multiple exostoses was not detected.
Interestingly in our case, the location of the lesion was the superior segment of the left lower lobe, an area that is typically not accessible by CP-EBUS, due to the size of the airway. With gentle manipulation of the bronchoscope, the probe was introduced into the segmental airway allowing the lesion to be visualized, characterized, and sampled. The diagnosis of chondrosarcoma was made from the cytology specimen from a 21-G needle without the need for further tissue sampling. This is contrary to the experiences published in the literature where larger histologic specimens are recommended to make the diagnosis of sarcomas.18,19
Taken together, the successful diagnosis of such rare tumors as sarcomas by CP-EBUS-TBNA modality indicates the growing importance of this minimally invasive technology.
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CP-EBUS-TBNA; chondrosarcoma; Maffucci syndrome
© 2014 by Lippincott Williams & Wilkins.
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