Follicular dendritic cell (FDC) sarcomas of the nasopharynx are rare tumours; only seven cases have been reported in the English language medical literature. The authors present an eighth case, which occurred in a 70-year-old woman whose main complaint was nasal obstruction. It has been more than 10 years since FDC sarcoma was reported to occur in extranodal sites, and clinical and pathological characteristics of extranodal FDC sarcomas remain to be defined. The lack of a high index of suspicion is the main reason for misdiagnosis. The authors point out the difficulties in the diagnosis and management of this rare condition.
Follicular dendritic cells (FDCs) are part of the accessory immune system and are normally found in the germinal centres of the secondary lymphoid follicles. Their main functions are the capture and presentation of the antigen and immune complexes, serving as antigen presenting cells and playing a major role in the induction and maintenance of the humoral immune response . According to the World Health Organization (WHO), FDC sarcomas are included in histiocytic and dendritic cell neoplasms . Many reports emphasize FDC sarcomas arising in lymph nodes , and as the morphologic features of FDC sarcomas have become better known, the possibility of this diagnosis is now commonly being considered, especially in nodal-based tumours. FDC sarcoma in extranodal sites seems to be much less recognized, and is generally not considered in the clinical or pathological differential diagnosis of extranodal sites. The authors present a case of FDC sarcoma and emphasize the difficulties associated with the diagnosis and management of the disease.
A 70-year-old woman was admitted with a nasal obstruction of 5 months’ duration. During clinical examination a mass was discovered in the nasopharynx that was red-brown in colour and approximately 3 cm × 3 cm × 2 cm in size. There was no ulceration or bleeding focus on it. Computed tomography and magnetic resonance imaging findings disclosed a nasopharyngeal mass without invasion to the clivus or parapharyngeal spaces ( Fig. 3 ). No problems with the cranial nerves were detected in the clinical examination. The patient requested minimally invasive surgery for the nasal obstruction, and rejected postoperative radiotherapy or chemotherapy. The authors performed curettage of the nasopharyngeal mass as in adenoidectomy and then endoscopically visualized the nasopharynx intraoperatively. There was free margin of tumour. Pathological examination of the specimen revealed proliferation of spindle to ovoid cells with whorled, storiform, and fusiform patterns ( Fig. 1 ). Immunohistochemically, the tumour cells expressed positivity for CD21, CD23, HLA-DR, fascin, and vimentin ( Fig. 2 ); they did not express muscle markers (smooth muscle actin, desmin, and muscle-specific antigen). The results were negative for epithelial markers (pancytokeratin, epithelial membrane antigen) and S-100 protein, as well as antibodies to CD68, CD34, CD20, CD3, and CD1a. Owing to the difficulty of achieving a disease-free space in the nasopharynx, the authors recommended external radiotherapy, but the patient rejected that option. Eight months later, positron emission tomography of the whole body detected no malignancy, locally or distantly.
Over the course of 3 years, the patient had two local recurrences and two local surgeries for them. The first recurrence was revealed in the 12-month follow up. Forty-6 months after the initial diagnosis, the patient has disease with advanced locoregional recurrence and multiple focuses with high fluorodeoxyglucose (FDG) positivity in the lungs and iliac bone, which were absent in previous examinations. She refuses any treatment other than the minimal surgery for relieving the nasal obstruction.
FDC sarcomas primarily affect the young or middle-aged adults. No gender predilection has been reported; however, a slight female predominance (1.2:1) with a median age of 41.5 years has been determined . The head and neck region is the most common location for extranodal FDC sarcomas, particularly the tonsils . FDC sarcoma of the nasopharynx is limited to 7 previously reported cases. According to the WHO classification of tumours of the hematopoietic and lymphoid tissues, these tumours belong to histiocytic and dendritic cell neoplasms .
Extranodal FDC sarcomas, like their nodal counterparts, typically have distinct histological, immunophenotypical, and ultrastructural findings that allow a definitive diagnosis . At least one of the following should be positive for an FDC diagnosis: CD 21, CD 35, CD 23, Ki-M4p, and CAN.42 . Clusterin is always strongly positive; in addition, desmoplakin, vimentin, fascin, EGF receptor, and HLA-DR are usually positive for FDC. FDC may show variable staining for epithelial membrane antigen (EMA), S 100 protein, and CD 68. Occasionally cytokeratin, CD 45, and CD 20 display positivity for FDC. But the following are precisely negative for FDC sarcomas: CD 1a, lyzozime, myeloperoxidase, CD 34, CD 33, CD 79 α, CD 30, and HMB 45 .
The lack of a high index of suspicion is the main reason this tumour is misdiagnosed, because FDC markers are not routinely used in immunohistochemical studies of poorly differentiated tumours. These tumours should be considered as being low- or intermediate-grade malignancy, and the prognosis seems to be good for patients who receive early treatment . Evolution can be marked by local recurrences and metastases to sites such as the lungs, liver, and lymph nodes . The local recurrence rate is at least 40%, and the metastatic rate is at least 25% . No deaths have been reported from FDC sarcoma of the nasopharynx . Owing to the short-term follow up periods in the reported cases, the local recurrence and metastatic rates might be underestimated.
Differential diagnosis of FDC includes ectopic meningioma, ectopic or orthotopic thymoma, undifferentiated carcinoma, malignant fibrous histiocytoma, large cell lymphoma, metastatic carcinoma, gastrointestinal tumours, and peripheral nerve sheath tumours .
Some authors have proposed the following criteria for poor prognosis: tumour size, nuclear pleomorphism, mitotic count, intra-abdominal location, lack of adjuvant therapy, coagulative necrosis, and significant cellular atypia . Other than cellular atypia, none of the factors mentioned above showed significant statistical power in predicting tumour recurrence, and it is questionable whether a more poorly differentiated FDC sarcoma will show a more aggressive clinical pattern .
To the best of the authors’ knowledge, there is no reported prospective study of treatments and results in patients with FDC sarcomas, owing to the low number of cases, so it can be considered normal to have controversies regarding treatment. As with any other sarcoma, resection of the tumour with a wide margin is generally recommended whenever feasible. As in this case, surgery alone generally does not provide disease-free survival. The authors want to highlight the importance of adjunctive treatment modalities. FDC sarcomas should be considered as intermediate-grade malignancies. In previous studies, all patients with disease of the nasopharynx had radiotherapy or chemotherapy in addition to surgery: all of the cases had surgery and postoperative radiotherapy except one that had neoadjuvant chemotherapy and surgery. Despite the authors’ urging, the patient in the present case is the first to have only one treatment modality. Although there have been no reported deaths from nasopharynx disease in the case studies, surgery does not seem to be enough to treat these patients, possibly due to the location, where it is difficult to achieve a wide free margin of tumour. Tumour behaviour may also be a factor, as FDC sarcomas, specifically extranodal ones, have a high incidence of local and distant metastasis.
The number of patients studied is not enough to produce a definitive decision, but it seems that the best course for FDC sarcoma patients with nasopharynx involvement is to have postoperative radiotherapy to prevent locoregional recurrences. If there are any predictors of aggression of the tumour, as previously described, systemic chemotherapy (neo- or adjunctive) can be added to treatment.