Primary paragangliomas of nasal cavity and paranasal sinus are rare conditions that could show aggressive behavior with local recurrence and metastasis development. The diagnosis of malignancy is challenging because there are no available histopathologic criteria. In these cases, the prognosis is usually poor.
We report a case of a woman with malignant paranasal sinus paragangliomas.
The patient was treated with several surgical approaches, radiotherapy, and medical therapy for different recurrences.
Despite the malignant behavior of the disease, this patient is still alive many years after first diagnosis.
Tumori 2016; 102(Suppl. 2): e9 - e11
Article Type: CASE REPORT
AuthorsLiliana Belgioia, Francesco Pupillo, Almalina Bacigalupo, Renzo Corvò
- • Accepted on 16/09/2015
- • Available online on 13/10/2015
- • Published online on 11/11/2016
This article is available as full text PDF.
Paragangliomas (PGLs) are slow-growing neuroendocrine neoplasms arising from paraganglionic tissue of the autonomic nervous system (1). Head and neck PGLs (HNPGLs) are rare, approximately 3% of all PGLs (2); the estimated clinical incidence is 1/100,000 patients per year (3). The most common HNPGLs are tympanic, jugular, vagal, and carotid PGLs; paranasal and nasal cavity are rare (4).
We report a case of a woman who presented to our institute in June 2012 to evaluate adjuvant radiation therapy for a right maxillary sinus recurrence of paragangliomas diagnosed around 20 years previously.
In April 1993, at age 53 years, a patient received a diagnosis of nasal cavity paragangliomas. She was treated with surgery in December 1994. After 10 years disease-free, she had a local recurrence in November 2003, treated again with radical surgery. In May 2004, she had an MRI owing to worsening headache and anosmia occurrence. The MRI showed evidence of a third recurrence with extension in anterior cranial fossa with mass effect but without dura mater infiltration. The patient underwent craniotomy with resection of lesion and subsequent adjuvant radiotherapy in another Italian center; in this first radiation treatment, she received a total dose of 48.6 Gy in 27 fractions on nasal cavity by 3D conformal radiotherapy technique. After 2 years, a fourth recurrence emerged, with obliteration of right maxillary sinus and emiarcata alveolaris. Between 2006 and 2008, the patient underwent 5 cycles of peptide receptor radionuclide therapy, alternating 177Lu-DOTATOC to 90Y-DOTATOC. After this treatment, the patient had stable disease until March 2012, when a fifth progression on maxillary sinus was evidenced by MRI (
3D Imaging at MRI of the fifth local recurrence treated with surgery followed by intensity-modulated radiotherapy.
After this surgery, she presented to our institute, where a new adjuvant radiation therapy was planned. Taking into account the previous radiotherapy, she was treated by helical tomotherapy with a total dose of 45 Gy in 20 fractions (20 Gy in 10 fractions + sequential boost 25 Gy in 10 fractions) to the gross tumor. Clinically negative neck nodes were not included in the radiation fields. This second radiation treatment was well-tolerated with the exception of low-grade zygomatic right edema, conjunctivitis, and erythema, treated with topical therapies.
In December 2012, the patient presented lateral cervical lymphadenomegalia and underwent left nodes dissection with confirmation of tumor metastasis. In January 2014, a control computed tomography (CT) scan evidenced further right maxillary recurrence and lateral cervical nodes localizations. The patient started therapy with sunitinib 50 mg/d with partial response after 2 cycles: however, she referred a worsening quality of life owing to mucositis and persistent fatigue with neutropenia, so she continued sunitinib at a dose of 25 mg/d. In November 2014, a CT showed new progression of disease on neck nodes and in maxillary sinus; she started a new therapy with temozolomide with limited benefit. In August 2015, 22 years after the initial diagnosis, the patient evidenced stable nodal disease but was under careful evaluation for further radiotherapy on the primary site in case of new disease-related symptoms.
Head and neck PGLs are rare tumors, with a female predominance, most frequently diagnosed in middle-aged adults (mean age 41-47 years); genetic cases (linked mainly to 4 genetic syndromes, all with autosomal dominant transmission) are more than a decade younger (4). At diagnosis, our patient was 53 years old. She had not undergone genetic testing but she did not report any other case in her family so her case was most likely sporadic.
Paranasal and nasal cavity PGLs are exceptional tumors; a review of the literature reveals about 40 cases of PGLs arising from this site, comprehensive both of benign and malignant forms. Even if most of PGLs are benign, about 10%-15% are malignant; nasal PGLs often behave aggressively locally, recurrence is common, and metastasis can occur (4). Malignancy in paragangliomas is determined only if metastasis to non-neuroendocrine tissue is demonstrated (5). Histopathologic criteria for malignancy are not available; as a result, malignant behavior of such tumors is diagnosed on clinical grounds. Additional clinical signs for malignancy may be an aggressive course of disease with bone invasion or rapid development of recurrence (1). This is especially important for paragangliomas of the paranasal sinuses, since they metastasize in 24% of cases, whereas other paragangliomas of the head and neck region show malignant behavior in only 4%-16% (6). Our patient presented several local relapses and neck nodal metastasis, showing clear malignant behavior.
The management of patients with malignant HNPGLs should be directed toward complete surgical resection; radiotherapy can find a role in a radical setting where surgery is not feasible or in the postoperative setting where radiation may be useful in slowing the progression of residual disease. As regards systemic therapy, the results of chemotherapy are modest, but treatment with radiolabeled somatostatin analogs such as 90Y-DOTATOC and 177Lu-DOTATOC has shown benefit in a limited number of patients (7); in addition, targeted therapies have been introduced, of which especially sunitinib showed promising results in small series (8). The timing of systemic therapy in these patients is debated because a retrospective study in therapy-naive patients with malignant PGL has shown that nearly half of patients achieved stable disease at 1 year and that therefore, in symptom-free patients, a wait-and-scan surveillance policy until imaging progression seems appropriate as first-line treatment (4).
Our patient had undergone all these multimodality therapies, with alternating phases of stable disease with loco-regional progression. Her disease shows an indolent course but despite the clear malignant behavior she presents a long survival with an acceptable quality of life. No severe side effects were evident after the 45 Gy reirradiation carried out in 2012.
Although prognosis in individuals with recurring malignant PGL cannot be predicted, generally overall survival is poor, with 5-year survival rates reported in the literature of only 20%-50% (9, 10). Our patient is still alive 22 years after first diagnosis; this suggests that tailored treatments should be carefully adopted to control the HNPGL without inducing severe late effects, as a long course may be possible even if a malignant phenotype is predominant.
- Belgioia, Liliana [PubMed] [Google Scholar] 1, * Corresponding Author (email@example.com)
- Pupillo, Francesco [PubMed] [Google Scholar] 2
- Bacigalupo, Almalina [PubMed] [Google Scholar] 1
- Corvò, Renzo [PubMed] [Google Scholar] 1
Division of Radiation Oncology, AOU IRCCS San Martino-IST National Cancer Research Institute and University, Genoa - Italy
Division of Medical Physics, AOU IRCCS San Martino-IST National Cancer Research Institute and University, Genoa - Italy