Volume 6, Issue 2 , Pages 104-106, March 2011
Follicular dendritic cell sarcoma presenting in the submandibular region of an 11-year-old
Article Outline
Abstract
Follicular dendritic cell sarcomas are rare malignancies of antigen-presenting cells. Likely under-diagnosed, these sarcomas arise from the dendritic reticulum cells of lymph nodes. Extranodal presentations are rare, with fewer than 70 reported head and neck cases, most commonly involving the tonsils. We present a case of FDCS involving the submandibular region in an 11-year-old. To our knowledge, this is the third reported head and neck case in a patient under the age of 16. We review the differential diagnosis of this rare sarcoma and highlight key features differentiating FDCS from other poorly differentiated neoplasms to enable prompt diagnosis and appropriate treatment.
Keywords: Follicular dendritic cell sarcoma, Dendritic reticulum cells, Antigen-presenting cells, Submandibular, Pediatric
1. Introduction
Follicular dendritic cell sarcomas (FDCS), formerly known as follicular dendritic cell tumors, are rare and likely under-diagnosed malignancies arising from the dendritic reticulum cells of lymph nodes. Extranodal cases are rare, with fewer than 70 cases reported in the head and neck [1]. The tonsils are the most common extranodal site in the head and neck [2]. Other sites include the nasopharynx, parapharyngeal space, maxillary alveolar ridge, hard and soft palate [1]. FDCS typically affects young or middle aged patients and there may be a slight female predominance [3], [4]. We present the case of an 11-year-old patient with FDCS involving the right submandibular region. To our knowledge, in a patient under the age of 16, there have been only three prior reported case of FDCS in the head and neck.
2. Case report
An 11-year-old boy presented for evaluation following resection of a submandibular mass, thought to be a salivary gland cyst on pre-operative imaging. Frozen section at the time of surgery was favored to be an inflammatory lesion; however, the final pathology demonstrated a FDCS. He then presented to our institution and was closely followed for one year until he developed fullness of the right submandibular space. Fine needle aspiration demonstrated numerous polymorphous lymphocytes, consistent with reactive hyperplasia. Post-gadolinium T1-weighted MR imaging demonstrated uniform enhancement of the right submandibular gland and tumor and extension of the tumor along the buccal margin of the mandible into the subcutaneous fat (Fig. 1).
Fig. 1.
Axial post-gadolinium T1-weighted MR image shows uniform enhancement of the gland and tumor and extension of the tumor along the buccal margin of the mandible into the subcutaneous fat.
Given his history, the patient underwent exenteration of the right submandibular space (level 1) with removal of a 3-cm mass and associated facial lymph nodes. The marginal mandibular, hypoglossal, and lingual nerves were preserved. Pathology was consistent with recurrent FDCS. The tumor showed evidence of extensive infiltration of the fibroadipose tissue and skeletal muscle around the submandibular gland (Fig. 2), with focal involvement of the salivary gland parenchyma. The tumor exhibited a syncytial, swirling growth pattern (Fig. 3). The neoplastic cells had indistinct cell borders, a moderate amount of eosinophilic cytoplasm, and oval to elongated nuclei; there were rare mitoses and occasional multinucleate cells (Fig. 4). Immunohistochemical staining revealed a characteristic pattern for a FDCS – the tumor cells were diffusely positive for CD23, CD35, and fascin, with patchy strong staining for CD21 (Fig. 5). Many scattered small lymphocytes within the tumor stained for CD45 and there was some weak tumor cell staining for CD68. The tumor cells were negative for S-100, EMA, and CD1a.
Fig. 2.
FDCS showing neoplastic cells infiltrating skeletal muscle (H&E, ×600).
Fig. 3.
The tumor cells exhibit a syncytial, swirling growth pattern (H&E, ×400).
Fig. 4.
The neoplastic cells have eosinophilic cytoplasm, indistinct cell borders, and oval to elongated nuclei. Rare mitoses and occasional multinucleate cells are present (H&E, ×600).
Fig. 5.
The tumor is immunohistochemically positive for the follicular dendritic cell marker CD23 (×600).
The patient was treated post-operatively with proton beam radiotherapy because of positive microscopic margins and his history of recurrence. Over 29 months following salvage treatment, he continues to have no evidence of recurrence.
3. Discussion
Follicular dendritic cells (FDCs), also known as dendritic reticulum cells, are non-lymphoid elements found in the germinal centers of lymph nodes and other areas of the reticuloendothelial system [2], [3]. Although their exact mechanism is not known [5], FDCs are a major component in the humoral immune response via antigen presentation and antigen-dependent maturation of the B-cell immune response [1], [2]. Together with interdigitating dendritic cells and Langerhans cells, FDCs are the non-lymphoid and non-phagocytic accessory cells of the lymphoid system [5].
Although the existence of FDCS was hypothesized in 1978 by Lennert [7], the first reported case of malignant transformation from FDCs was not until 1986 when Monda et al. described four cases, each initially misdiagnosed [8]. FDCS are termed sarcomas to emphasize their distinction from lymphomas [2], [3], [9]. An estimated one-third of FDCS are initially misdiagnosed [4].
The etiology of FDCS is unknown. There is a reported association with the hyaline-vascular type of Castleman disease (HVCD) [2], [3], [4], [6] and a case report of serial biopsies showing transformation of HVCD to FDCS [1], [9]. Hepatic and splenic cases of FDCS are associated with the Epstein Barr Virus (EBV) [1], [3], [4], [5], [10]. Human herpes virus-8 has not been found to be related [1].
The differential diagnosis of FDCS includes non-lymphoid tissue-associated tumors such as ectopic meningioma, ectopic or orthotopic thymoma, undifferentiated carcinoma, malignant melanoma, malignant fibrous histiocytoma, inflammatory pseudotumor, angiosarcoma, hemangioendothelioma, large cell lymphoma and peripheral nerve sheath tumors [1], [2], [3]. Although the diagnosis of FDCS may be suspected histologically, it can only be confirmed immunohistochemically. The immunohistochemical profile of FDCS is unique, and helps to definitively distinguish FDCS from other entities in the differential diagnosis. Over 95% of FDCS's are positive for markers of follicular dendritic cells: CD21, CD23, and CD35 [1], [2], [7], [11]. They are typically positive for desmoplakin, vimentin and fascin [11] but are variably S100 protein or CD68 positive [4], [11]. They stain negative for CD45, CD20, CD1a, keratin, and HMB-45 [1], [11].
While ectopic meningiomas exhibit a swirling cellular pattern similar to FDCS, the presence of intranuclear pseudoinclusions and EMA immunohistochemical reactivity are not features of FDCS [3]. The lymphocytes typically in ectopic thymoma are immature T cells, rather than mature T cells as seen in FDCS [3]. Malignant melanoma is differentiated from FDCS because malignant melanoma stains positive for Mitf1, Mart-1. HMB-45, and diffusely for S-100 [3]. In malignant fibrous histiocytoma, the nuclei are more hyperchromatic and pleomorphic compared to the nuclei in FDCS and the syncytial and fibrillary quality noted in FDCS is not seen [3]. In inflammatory pseudotumor, more plasma cells are seen whereas nuclear atypia is not observed [3]. Angiosarcoma and hemangioendothelioma have intracytoplasmic vacuoles and lumens, and are positive for endothelial markers, such as CD31 and CD34, but lack a lymphocytic component [3]. The nuclei in malignant peripheral nerve sheath tumors are more elongated, buckled and hyperchromatic and these tumors lack a lymphocytic component as well [3]. FDCS must also be differentiated from neoplasms arising from the major subtypes of reticulum cells: interdigitating dendritic cells, dendritic cells and fibroblastic reticular cells [2]. Misdiagnosis is common unless immunohistochemical markers are used.
FDCS cannot be reliably distinguished from other malignancies radiographically [1]. On CT, invasion of bone or local soft tissue structures may be evident [1]. MR imaging may show an expansive process that is isointense on T1-weighted images, hyperintense on T2-weighted images and that enhances after gadolinium administration [1].
Grossly, FDCS appear as pink, white, and/or tan-gray solitary, well-circumscribed solid tumors with defined margins owing to their pushing growth pattern [1], [3], [11]. A key feature histologically is the syncytial arrangement of oval to spindled eosinophilic cells with indistinct cell boundaries and distinct nucleoli [2], [3], [5], [11]. As in the case presented here, multinucleated cells can also be seen. A storiform arrangement with admixed lymphocytes is the most characteristic growth pattern [1], [4], but other patterns including whorled, fascicular, diffuse, and trabecular are also described [5], [6]. In some cases, FDCS may appear fibrillary because of its close interdigitating cell processes [2]. Small lymphocytes intermixed with tumor cells around blood vessels, known as perivascular cuffing, is a characteristic finding [1], [3], [5].
FDCS are considered to be low to intermediate grade malignancies [2], [3] with indolent clinical courses, similar to that of low-grade tissue sarcomas [11]. Most cases are treated with surgical resection [2], [3], [11]. Radiotherapy and/or adjuvant chemotherapy is used for residual or recurrent disease [3], but has not been shown to increase long-term survival [2]. Recurrence is likely under-appreciated for the same reasons primary FDCS is under-diagnosed [3]. Local-regional recurrence is as high as 40% and the distant metastatic rate is approximately 25%, with metastases to the liver, lung, peritoneum and lymph nodes reported [9], [11]. The clinical course if often very long, but eventually, as many as 20% of patients succumb to the disease [3], [11].
4. Conclusion
FDCS is a rare, often misdiagnosed malignancy of antigen-presenting cells that can occur in either nodal or extranodal sites, most commonly of the head and neck. Since the first reported cases in 1986, advances in immunohistochemistry and broader awareness of this tumor has increased our ability to diagnose these rare malignancies. Extranodal cases are especially uncommon, with just under 70 cases reported in the head and neck, most involving the tonsil. The application of FDCS immunohistochemical markers is critical to making an accurate diagnosis, and thereby minimize morbidity associated with unnecessary work-up and treatment. Recurrence and metastatic disease are common, requiring close follow-up with possible salvage surgery and post-operative radiation therapy.
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PII: S1871-4048(10)00044-4
doi:10.1016/j.pedex.2010.05.010
© 2010 Elsevier Ireland Ltd. All rights reserved.
Volume 6, Issue 2 , Pages 104-106, March 2011
