Dendritic cell tumor in a salivary gland lymph node: a rare differential diagnosis of salivary gland neoplasms

  • Sebastian P Schraven1, 5Email author,

    Affiliated with

    • Stefan K Plontke2,

      Affiliated with

      • Roland Syha3,

        Affiliated with

        • Falko Fend4,

          Affiliated with

          • Hartwig Wolburg4 and

            Affiliated with

            • Patrick Adam4

              Affiliated with

              Diagnostic Pathology20116:94

              DOI: 10.1186/1746-1596-6-94

              Received: 3 August 2011

              Accepted: 30 September 2011

              Published: 30 September 2011

              Abstract

              Dendritic cell tumors are extremely rare neoplasms arising from antigen-presenting cells of the immune system. We report a case of a 69-year-old man with an unremarkable medical history who presented with a 2-months history of a gradually enlarging painless, firm, mobile, 2 × 2-cm swelling at the caudal pole of the left parotid gland without systemic symptoms. Histologically, the tumor consisted of a spindle cell proliferation in an intraparotideal lymph node. Based on the histopathologic, immunohistochemical and electron microscopic findings, a dendritic cell tumor, not otherwise specified (NOS) in an intraparotideal lymph node was diagnosed.

              The patient underwent complete tumor resection, and is currently free of disease, 2 years after surgery. These extremely rare tumors must be distinguished from other more common tumors in the salivary glands. Awareness that dendritic cell tumors may occur in this localization, careful histologic evaluation and ancillary immunohistochemical and electron microscopical analyses should allow for recognition of this entity.

              Keywords

              Dendritic cell tumor salivary gland lymph node

              Background

              Dendritic cell sarcomas (DCS) are exceedingly rare entities, arising from antigen-presenting cells of the immune system. DCS are subclassified into the better characterized follicular (FDCS) [1] and interdigitating (IDCS) [2] dendritic cell sarcomas and other rare and less well classifiable dendritic cell tumors like fibroblastic reticular cell tumors, indeterminate dendritic cell tumors and dendritic cell tumors, not otherwise specified (DCT, NOS) [2]. DCS was first described in 1986 by Monda et al. [3]. Since then, nearly 300 cases, most of them FDCS, have been described in the literature. Although most DCS evolve in cervical, mediastinal, axillary and inguinal lymph nodes, also extranodal manifestations have been described [4]. The clinical behaviour of DCS is similar to that of low-grade soft tissue sarcoma, with an approximately 30% overall risk for developing local recurrences and metastases [5]. Because of the rareness of the disease a standardized treatment is lacking.

              We herein report a case of a dendritic cell tumor, NOS of an intraparotideal lymph node, emphasizing the important role of ancillary immunohistochemical and molecular studies in establishing this extraordinarily rare diagnosis.

              Case report

              A 69-year-old man presented with a 2-months history of a gradually enlarging painless, firm, mobile, 2 × 2 × 2 cm swelling at the caudal pole of the left parotid gland without systemic symptoms. His medical history was unremarkable.

              Magnet resonance imaging (MRI) showed a 2 × 2 × 2 cm mass with hyperintense signal on T2-weighted images and hypointense signal on T1-weighted sequences and a contrast enhancement which bordered directly to the lateral part of left sternocleidomastoid muscle and displaced the external jugular vein dorsally. Cranially there was no clear demarcation to the left parotid gland (Figure 1). The patient underwent surgical excision of the swelling by a partial left parotidectomy with preservation of the facial nerve. Because of insecure R0-status a follow-up resection with extended partial parotidectomy and ipsilateral selective neck dissection (levels II and III) was conducted. A primary tumor of the upper aerodigestive tract was excluded by panendoscopy. Subsequent total body positron emission tomography with 18-F-fluorodesoxyglucose and computed tomography scan 6 months after surgery were unremarkable. The patient is currently disease free, 2 years after surgery.
              http://static-content.springer.com/image/art%3A10.1186%2F1746-1596-6-94/MediaObjects/13000_2011_477_Fig1_HTML.jpg
              Figure 1

              Axial MR image. (T2-weighted) of a 2 × 2 cm mass with hyperintense signal (arrow) directly bordering the lateral part of left sternocleidomastoid muscle (asterisk) and displacing the extern jugular vein (arrow head) dorsally. Cranially there was no clear demarcation to the left parotid gland.

              Material and methods

              The specimen was fixed in 10% buffered formalin, paraffin-embedded, and histologic sections were obtained. Sections were routinely stained with hematoxylin and eosin. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections on an automated immunostainer (Ventana Medical Systems©, Tucson AZ) following the manufacturer's protocols. The monoclonal antibodies used are listed in Table 1.
              Table 1

              List of antibodies and staining results.

              Antibody

              Company

              Dilution

              Tumor cells

              Vimentin

              DAKO

              1:1000

              positive

              HLA-DR

              DAKO

              1:200

              part.positive

              Fascin

              Abcam

              1:100

              positive

              Langerin

              eBioscience

              1:50

              negative

              Lysozym

              DAKO

              1:400

              negative

              S100

              DAKO

              1:5000

              negative

              AE1/3

              DAKO

              1:100

              negative

              HMB45

              DAKO

              1:50

              negative

              MITF

              Zytomed

              1:100

              negative

              PMZ

              Zytomed

              1:50

              negative

              LCA

              DAKO

              1:500

              negative

              Calponin

              DAKO

              1:200

              negative

              Caldesmon

              DAKO

              1:50

              negative

              Clusterin

              Menarini

              1:30

              negative

              EMA

              DAKO

              1:100

              negative

              SMA

              DAKO

              1:500

              negative

              CK5/6

              DAKO

              1:100

              negative

              CK8/18

              Zytomed

              1:100

              negative

              OSCAR

              Zytomed

              1:200

              negative

              Synaptophysin

              DCS

              1:200

              negative

              Chromogranin

              DAKO

              1:500

              negative

              Factor XIIIa

              DCS

              1:100

              negative

              CD1a

              DAKO

              1:50

              negative

              CD3

              Santa Cruz

              1:200

              negative

              CD4

              Zytomed

              1:200

              negative

              CD20

              DAKO

              1:500

              negative

              CD21

              Zytomed

              1:50

              negative

              CD23

              Novocastra

              1:30

              negative

              CD30

              DAKO

              1:50

              negative

              CD31

              DAKO

              1:100

              negative

              CD34

              DAKO

              1:50

              negative

              CD35

              Novocastra

              1:50

              negative

              CD56

              Cell Marque

              1:100

              negative

              CD68 (PG-M1)

              DAKO

              1:200

              negative

              CD117

              DAKO

              1:200

              negative

              CD123

              BD Pharmingen

              1:50

              negative

              Mib1

              DAKO

              1:200

              40-50%

              For electron microscopical (EM) evaluation, small pieces of tissue were dissected out of the paraffin bloc, rehydrated stepwise and postfixed in 1% OsO4 in 0.1 M cacodylate buffer (pH 7.4) and then again dehydrated in an ethanol series (50, 70, 96, 100%). The 70% ethanol was saturated with uranyl acetate for contrast enhancement. Dehydration was completed in propylene oxide. The specimens were embedded in Araldite (Serva©, Heidelberg, Germany). Ultrathin sections were produced on a FCR Reichert Ultracut ultramicrotome (Leica©, Bensheim, Germany), mounted on pioloform-coated copper grids, contrasted with lead citrate and analyzed and documented with an EM10A electron microscope (Carl Zeiss©, Oberkochen, Germany). The pictures were digitized and processed with Adobe Photoshop.

              Results

              Gross and histological findings

              The specimen consisted of parotid gland tissue containing a single firm, nodule 2.3 cm in diameter. The cut surface was soft and homogeneous light-grey. Microscopic examination revealed a spindle cell neoplasia in an intraparotideal lymph node. Tumor cells featured moderate nuclear pleomorphism, bulked chromatin and a clearly perceptible nucleolus (Figure 2A, B). Furthermore an elevated mitotic rate (up to 27 mitoses per 10 high power fields) was found.
              http://static-content.springer.com/image/art%3A10.1186%2F1746-1596-6-94/MediaObjects/13000_2011_477_Fig2_HTML.jpg
              Figure 2

              Morphology and immunohistochemical stainings: (A) H&E (original magnification 100×) and (B) H&E (original magnification 400×) show a spindle cell proliferation in an intraparotideal lymph node with moderate cellular pleomorphy (C) Vimentin (original magnification 400×) and (D)HLA-DR (original magnification 400×) were strongly expressed by the tumor cells. (E) Clusterin (original magnification 400×) and (F) S100 protein (original magnification 400×) were negative in the tumor cells. (G)CD20 showed only very few reactive small B-cells (original magnification 400×) and (H) CD3 some reactive T-lymphocytes (original magnification 400×). Virtual Slides: http://​diagnosticpathol​ogy.​slidepath.​com/​dih/​webViewer.​php?​snapshotId=​1316777507, http://​diagnosticpathol​ogy.​slidepath.​com/​dih/​webViewer.​php?​snapshotId=​1316777681, http://​diagnosticpathol​ogy.​slidepath.​com/​dih/​webViewer.​php?​snapshotId=​1316777716, http://​diagnosticpathol​ogy.​slidepath.​com/​dih/​webViewer.​php?​snapshotId=​1316777754, http://​diagnosticpathol​ogy.​slidepath.​com/​dih/​webViewer.​php?​snapshotId=​1316777781

              Immunohistochemical Findings

              To further characterize the histogenesis of this tumor, immunohistochemical stainings were performed. The tumor cells were positive for vimentin, fascin and HLA-DR (Figure 2B, D). In contrast, the neoplastic cells were negative for all epithelial, melanocytic, lymphoid, histocytic and follicular dendritic cell markers used. The proliferation, as assessed by Mib1 index was 40-50%. The results of the immuohistochemical stainings are shown in table 1.

              Electron Microscopic Findings

              The electron microscopical aspect of the tissue was characterized by cells which were devoid of characteristic structures as desmosomes or Birbeck granules. There was a certain heterogeneity of nuclei concerning their amount of heterochromatin. However, the cytoplasm of the cells (size, content of mitochondria or endoplasmatic reticulum) was less well differentiated (Figure 3A). The most prominent finding was the large number of slender long-spacing collagen fibers dividing the tissue in many compartments (Figure 3A). Fibrous long-spacing collagen the period length of which was in the order of 200 nm in this case (Figure 3B), is not described in the literature to be specific for any disease, but has been found in a variety of normal and pathological tissues. Therefore, it cannot be used as a pathognomonic marker here.
              http://static-content.springer.com/image/art%3A10.1186%2F1746-1596-6-94/MediaObjects/13000_2011_477_Fig3_HTML.jpg
              Figure 3

              Electron microscopy (EM): Most prominent feature was the large number of slender long-spacing collagen fibers dividing the tissue in many compartments (A). Fibrous long-spacing collagen the period length of which was in the order of 200 nm in this case (B), is not described in the literature to be specific for any disease, but has been found in a variety of normal and pathological tissues. Well-formed desmosomes or Birbeck granules were not found in this case.

              In summary, the morphological and immunophenotypic features were consistent with a dendritic cell tumor, not otherwise specified (NOS) originating in an intraparotideal lymph node. A differentiation towards a follicular or interdigitating dendritic cell sarcoma could not be demonstrated.

              Conclusions

              Dendritic cell sarcomas (DCS) are rare neoplasms arising from antigen-presenting cells of the immune system [2]. DCS are being recognized with an increasing frequency. These tumors can occur, where dendritic cells are located. One of the most common manifestation sites are the head and neck region. Under-recognition of this entity may contribute to its rarity. The WHO subclassifies DCS into five groups [2]: Langerhans cell histiocytosis, Langerhans cell sarcoma, interdigitating dendritic cell sarcoma (IDCS), follicular dendritic cell sarcoma (FDCS) and other rare and less well classifiable dendritic cell tumors like fibroblastic reticular cell tumors, indeterminate dendritic cell tumors and dendritic cell tumors, not otherwise specified (DCT, NOS) [2]. FDCS is the most common subtype followed by IDCS.

              The clinical course of this neoplasia is similar to that of soft tissue sarcomas [3, 6]. Since only 306 cases of DCS have been reported worldwide (table 2), there is no general consensus on the treatment of this rare disease. Surgery has remained the gold standard in localized disease, but a recurrence rate up to 50% has been reported [5]. Alternatively some DCS have also been treated additionally by radiotherapy and or chemotherapy [7]. For our patient we chose the option of surgical therapy and he is well and free of disease for 2 years after surgery now.
              Table 2

              Overview of dendritic cell sarcoma case reports.

               

              FDCS

              IDCS

               

              1986 - 4/2007 *

              Nodal

              77

              33

              110

              Extranodal

              52

              22

              74

              5/2007 - 08/2011 [5, 7, 1086]

              Nodal

              68

              14

              82

              Extranodal

              33

              7

              40

               

              230

              76

              306

              FDCS, follicular dendritic cell sarcoma; IDCS, interdigitating cell sarcoma. * Modified from [5]. A total of 145 nodal FDCS cases, 85 extranodal FDCS cases, 47 nodal IDCS cases and 29 extranodal cases have been reported until 08/2011. 2 cases FDCS and 2 cases of IDCS occured in the parotid gland.

              For establishing the diagnosis a large number of immunohistochemical stainings and ultrastructural analyses has been performed. Other rare differential diagnosis of salivary glands, like lipomatous pleomorphic adenoma [8] or sebaceous adenoma [9], were excluded. Despite this extensive work-up a definite assignation to an established entity of dendritic cell tumors could not be achieved. Therefore a diagnosis of dendritic cell tumor, NOS was made.

              In summary, we report on the clinical, pathologic, and immunohistochemical features of a dendritic cell tumor, NOS in an intraparotideal lymph node. Metastatic disease was ruled out by PET- and CT imaging. Recognition of this extremely rare tumor, and its distinction from more common malignant tumors of lymph nodes and salivary glands largely depends on judicious application of immunohistochemical and ultrastructural techniques. The precise histogenesis of these extraordinarily rare tumors remains to be established.

              Consent

              Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

              Declarations

              Acknowledgements

              This publication was funded by the German Research Foundation (DFG) and the University of Wuerzburg in the funding programme Open Access Publishing.

              Authors’ Affiliations

              (1)
              Department of Otolaryngology, Head and Neck Surgery, University of Tübingen
              (2)
              Department of Otolaryngology, Head and Neck Surgery, University of Halle-Wittenberg
              (3)
              Department of Diagnostic and Interventional Radiology, University of Tübingen
              (4)
              Institute of Pathology and Comprehensive Cancer Center (CCC), University of Tübingen
              (5)
              University of Würzburg, Department of Otolaryngology, Head and Neck Surgery

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              This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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