- Email: [email protected]
Indeterminate Dendritic Cell Tumor in Thoracic Spine: A Case Report
Accepted Manuscript Indeterminate Dendritic Cell Tumor in Thoracic Spine: A Case Report and Review of Literature Sze Kiat Tan, BS, Lee Onn Chieng, BS, Karthik Madhavan, MD, Andrew Rosenberg, MD, Ian Cote, MD PII:
S1878-8750(17)31176-2
DOI:
10.1016/j.wneu.2017.07.076
Reference:
WNEU 6138
To appear in:
World Neurosurgery
Received Date: 20 March 2017 Revised Date:
12 July 2017
Accepted Date: 13 July 2017
Please cite this article as: Tan SK, Chieng LO, Madhavan K, Rosenberg A, Cote I, Indeterminate Dendritic Cell Tumor in Thoracic Spine: A Case Report and Review of Literature, World Neurosurgery (2017), doi: 10.1016/j.wneu.2017.07.076. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT S.K. Tan et al. Indeterminate Dendritic Cell Tumor in Thoracic Spine: A Case Report and Review of Literature
Cote, MD1
Department of Neurological Surgery
SC
1
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Sze Kiat Tan, BS1, Lee Onn Chieng, BS1, Karthik Madhavan, MD1, Andrew Rosenberg, MD2, Ian
and the Miami Project to Cure Paralysis Department of Pathology
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2
University of Miami Miller School of Medicine Miami, Florida, USA.
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Authors’ emails: Sze Kiat Tan – [email protected]
Lee Onn Chieng – [email protected]
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Karthik Madhavan – [email protected] Andrew Rosenberg – [email protected]
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Ian Cote – [email protected]
Corresponding author: Ian Cote MD
University of Miami MILLER School of Medicine Department of Neurological Surgery
1
ACCEPTED MANUSCRIPT S.K. Tan et al. Lois Pope Life Center 1095 NW 14th Terrace (D4-6)
305-256-4492
Fax:
305-243-3337
Email:
[email protected]
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Telephone:
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Miami, FL 33136
Keywords: Birbeck granules
•
Epidermotropism
•
Histiocytic sarcoma
•
Indeterminate dendritic cell tumor
•
Langerin
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•
Abbreviations and Acronyms: DC: Dendritic cells
•
FISH: Fluorescence in situ hybridization
• •
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•
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•
H&E: Hematoxilin and eosin IDCT: Indeterminate dendritic cell tumor LCH: Langerhans cell histiocytosis
•
MRI: Magnetic resonance imaging
•
NLCH: Non-Langerhans cell histiocytosis
Running title – Indeterminate Dendritic Cell Tumor
2
ACCEPTED MANUSCRIPT S.K. Tan et al. Abstract Indeterminate dendritic cell tumor (IDCT) is an extremely rare hematological disorder with poorly understood pathogenesis. Occasionally encountered by hematologists, unusual
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presentations of IDCT have never been reported in the spine literature. The authors report a case of a 51-year-old man who presented with progressively worsening axial thoracic back pain radiating to his sides for three months. MRI revealed a large 3-cm enhancing mass at the T9
SC
vertebral body with an exophytic component causing significant canal stenosis. Initial percutaneous biopsy revealed histiocytic sarcoma. The patient underwent exploratory
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throracotomy and en-bloc resection of the lesion with T8-10 fusion. Interestingly, the final pathology results revealed IDCT with fibrosis. IDCT immunostaining was partially positive for Langerhans cell marker (positive for S100 and CD1a, but lacked Birbeck granules and Langerin stain) and partially for blastic plasmacytoid dendritic cell neoplasm. In addition, it was positive
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for CD45, CD68 and CD163. Lymphadenopathy is absent in this patient. Although first reported in the 1980s, IDCT has been omitted from most classifications due to its rarity. Rezk et al. (2008), reported 5 cases of IDCT which is usually restricted to the skin and lymph nodes and
EP
carried a good prognosis. Hematologists have debated the cell of origin; it is believed to be comprised of pre-Langerhans cells, as Birbeck granules are acquired after migration to the
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epidermis. As for now, IDCT remains of indeterminate origin. We report the first case of spinal IDCT, and familiarity with the histological features are warranted to ensure accurate diagnosis and appropriate treatment.
3
ACCEPTED MANUSCRIPT S.K. Tan et al. INTRODUCTION Indeterminate dendritic cell tumor (IDCT), comprised of so-called dermal indeterminate cells, is an extraordinary rare hematological neoplastic disorder.5,7 First noted by Wood et al. in 1985, it
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is an altered homing mechanism of proliferation of antigen-presenting dendritic cells.5 Due to its rarity, the proposed etiology of IDCT is unknown, although the most frequently discussed possibilities are extrinsic stimulations and association with low grade B-cell lymphoproliferative
SC
disorder.3,5 The pathophysiology has not been completely understood and hence often leads to
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misdiagnosis.
IDCT can develop in any population with no particular predilection for certain age or gender.7 The most common area of presentation of IDCT is usually skin, because these cells predominantly reside in the skin and lymph nodes.6 The skin of trunk and extremities are usually
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affected.4 There are three main types of dendritic cells (DC) in the human body that have been described, namely dermal DC expressing CD1a, dermal DC expressing CD14 and Langerhans cells expressing CD1a.4 Originating from the same progenitor cell, Rowden et al. suggested that
EP
indeterminate cells are pre-Langerhans cells that fail to complete their acquisition of Birbeck granules while migrating towards epidermis.8 Therefore, the major difference between these
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dendritic cells is the presence of ultrastructure Birbeck granules in the IDCT cells.5 In addition, IDCT cells will stain CD1a and S-100 protein but not CD207 (langerin) immunohistologically.5
We describe our experience with the management of a case of IDCT in the thoracic spine, as compared to skin and lymph nodes cases that are often found in the past literature. This is
4
ACCEPTED MANUSCRIPT S.K. Tan et al. essential in spinal surgery as the familiarity with the histological features are warranted to ensure
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accurate diagnosis and appropriate treatment of this rare entity.
CASE REPORT History and Examination
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A 51-year-old man presented with progressively worsening axial thoracic back pain radiating to his sides for three months. The pain was not associated with paresthesia or weakness. Patient
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denied any cutaneous or systemic symptoms. There was no lymphadenopathy noted. Extensive serological laboratory workups of patient were normal.
Imaging Studies
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Magnetic resonance imaging (MRI) revealed a large 3-cm enhancing mass at the T9 vertebral body with an exophytic component causing significant canal stenosis with epidural extension (Fig. 1). A CT angiogram of the chest showed the presence of an artery of Adamkiewicz at the
EP
level of the lesion. Subsequent PET scan of whole body confirmed low-level FDG avid bilateral cervical subcentimeter nodes, likely reactive. Initial percutaneous needle biopsy showed
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histiocytic sarcoma.
Operation
The patient underwent a right exploratory thoracotomy and en-bloc resection of the lesion with T8-10 posterolateral instrumented fusion using expandable titanium cage and rib autograft. 7th rib is also partially resected.
5
ACCEPTED MANUSCRIPT S.K. Tan et al. Pathological Examination The histopathological examination of the 4.5 × 3.7 × 2.1-cm resected mass revealed indeterminate dendritic cell tumor with fibrosis, chronic inflammation and reactive woven bone
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formation. The mass was an irregularly shaped lytic tumor-like lesion with no clear laterality. It mainly involved the middle as well as posterior aspects of the vertebral body, and extended through the cortex into the adjacent soft tissues. All inked resection margins were negative, and
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the clearance to the closest soft tissue margin was less than 0.1cm.
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The neoplasm was unusual and was composed of a multinodular proliferation of large histiocytelike cells with hyperlobulated nuclei that had smooth to irregular contours (Fig. 2 and 3). The cytoplasm of tumor cells was eosinophilic and abundant. The tumor cells demonstrated limited cytologic atypia, minimal mitotic activity and no necrosis. The lesional cells were admixed with
4).
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macrophages with significant lymphoblastic infiltration and surrounded by reactive fibrosis (Fig.
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Immunohistochemistry shows that the lesion cells are positive for CD1a, CD45, CD68 and CD163 (pale), and focally express Oct 2 (dim nuclear staining) as well as S100 (Fig. 5). The
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cells stained negative for Langerin, CD30, CD3, CD20, CD21, CD23, CD35, kappa and lambda light chains, tryptase, keratin, CK8/18, EMA, SALL4, BRAF and desmin. The proliferation rate estimated from the Ki67 stain is low and is less than 2%. This staining pattern is very consistent with an indeterminate dendritic cell tumor. Having abundant tissues to examine this time, the interpretation of malignancy was not warranted although the initial needle percutaneous biopsy was interpreted as representing histiocytic sarcoma.
6
ACCEPTED MANUSCRIPT S.K. Tan et al.
Postoperative Course The patient’s immediate
postoperative neurological examination remained unchanged. He
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recovered uneventfully and was discharged to home on postoperative day 12. On the third month post-operation, he continued to be symptoms free and the postoperative X-ray and CT
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demonstrated stable spinal construct and arthrodesis (Fig. 6, 7 and 8).
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DISCUSSION
To our best knowledge, this is the first reported case of IDCT in the spine as it usually presents as cutaneous neoplasm with multiple disseminated papules, nodules or plaques on skin in the absence of clinical manifestations.1,5 In the 2016 World Health Organization (WHO)
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Classification of Neoplasms of the Hematopoietic and Lymphoid tissues, nine types of dendritic cell neoplasms are listed: histiocytic sarcoma, Langerhans cell histiocytosis (LCH), Langerhans cell sarcoma, IDCT, follicular dendritic cell sarcoma, interdigitating dendritic cell sarcoma,
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fibroblastic reticular cell tumor, disseminated juvenile xanthogranuloma and Erdheim-Chester disease.9 On the other hand, Oh et al. described another classification of cutaneous histiocytic
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proliferation based on the immunophenotypic characteristics of lesional cells, namely “factor XIIIa-CD68+CD163+ macrophage, factor XIIIa+CD68+S100-CD1a- dermal dendritic cells, factor XIIIa-S100+CD1a+ LCs with Birbeck granules, and factor XIIIa-S100+CD1a+ indeterminate cells without Birbeck granules”.4
7
ACCEPTED MANUSCRIPT S.K. Tan et al. IDCT cells are hypothesized to belong to the family of myeloid cells.5 This is supported by the reported cases of antecedent as well as concurrent low-grade B-cell lymphoma in some patients.5 It is of interest to note that fluorescence in situ hybridization (FISH) demonstrated that both
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histiocytic/dendritic neoplasm and B-cell lymphoma express identical heavy chain gene rearrangements.5 The myeloid cells can differentiate through either antigen-presenting pathway or antigen-processing pathway to become colony-forming unit (CFU)-granulocytic/monocytic
SC
cells and CFU-dendritic cells respectively depending on the presence of specific cytokines.5 Langerhans cells and interstitial dendritic cells are later developed from the immature dendritic
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cells.5
Due to the unclear pathobiology of IDCT and its similarity to LCH, it is essential to be able to differentiate these diseases and treat them accordingly. Morphologically, IDCT cells possess
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long dendritic processes that are interdigitating with the processes of other IDCT cells.5 They also contain a high number of cytoplasmic organelles, but not Birbeck granules. In 1961, Birbeck et al. first reported this “tennis-racket” appearance organelles under the electron microscope that
EP
play a significant role in endocytosis.10 Langerin is a type II membrane-associated C-type lectin that is closely related to the Birbeck granules.2,10 It is also postulated that the IDCT cells are pre-
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Langerhans cells and they are arrested before acquisition of Birbeck granules during their transition from dermal to epidermal regions, possibly after their cell receptors interact with an epidermis-specific ligand.1,5 Therefore, the immunostaining for CD1a, CD68 and S100 are positive in both IDCT and Langerhans cells, but negative for CD207 in IDCT cells.5 This is the main characteristic that is used in diagnosis to distinguish between IDCT cells and Langerhans cells. On the other hand, non-Langerhans cell neoplasms (NLCN) such as Rosai-Dorfman
8
ACCEPTED MANUSCRIPT S.K. Tan et al. disease, juvenile xanthrogranuloma, multicentric reticulohistiocytosis, histiocytic sarcoma and Erdheim-Chester disease do not show the uniform expression of both S100 protein and CD1a.7,11
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Furthermore, CD1a is weakly and only focally expressed in NLCN.1
As compared to Langerhans cells, IDCT lesional cells usually lack of eosinophils and epidermotropism with microabscesses that are more typical for LCH.5 Hematoxilin and eosin
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(H&E) stain is unable to differentiate between these cells because of their close resemblance. Thus, the use of immunohistochemistry and electron microscope for the confirmation of IDCT
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and LCH is widely utilized, and remains the only modality to differentiate the two.
No standardized therapeutic regimen has been established for patients with IDCT. For cutaneous IDCT with single lesion, total resection by surgery is usually recommended.3 However, systemic
fluorouracil,
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treatment such as electron beam therapy, narrow-band ultraviolet, electrodessication, topical 5thalidomide, and low dose methotrexate have been suggested for those who
presented with generalized skin lesions.1,3 5% pure coal tar is also effective in pediatric patient.6
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There are also reported cases of spontaneous self-regression without treatment.3 The close follow-up of cases has found that the clinical course of IDCT is very indolent and usually self-
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limiting.3
It is extremely important to include LCH and Langerhans cell sarcoma in the differential diagnosis during the work-up. The ability to distinguish these entities is vital, as erroneously identifying IDCT as LCH can lead to overly aggressive management when more conservative measures are sufficient. The prognosis of IDCT is variable.3 Although in rare cases it can
9
ACCEPTED MANUSCRIPT S.K. Tan et al. progress to leukemia, there is no mortality case due to IDCT so far.6,7 In our case, surgical removal of the tumor is still deemed to be the best option for our patient even though the final
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diagnosis of IDCT was only discovered after resection of tumor mass.
In summary, IDCT is an extraordinarily rare malignancy that tends to be neglected in differential because of that. This is essential in spinal surgery as the familiarity with the histological features
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is warranted to ensure accurate diagnosis and appropriate treatment. Langerin (CD207) immunonegativity and the absence of Birbeck granules on electron microscopy for definite
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diagnosis must be shown, and the patient needs to be monitored closely with follow-ups.7
Conflict of interest statement: The authors report no conflicts of interest concerning the materials or methods used in this study or the findings specified in this paper.
Acknowledgements: No
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ACCEPTED MANUSCRIPT S.K. Tan et al. REFERENCES:
7. 8.
9.
10.
11.
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6.
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5.
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4.
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3.
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2.
Bakry OA, Samaka RM, Kandil MA, Younes SF: Indeterminate cell histiocytosis with naive cells. Rare Tumors 5:e13, 2013 Mizumoto N, Takashima A: CD1a and langerin: acting as more than Langerhans cell markers. J Clin Invest 113:658-660, 2004 Mo X, Guo W, Ye H: Primary Indeterminate Dendritic Cell Tumor of Skin Correlated to Mosquito Bite. Medicine (Baltimore) 94:e1443, 2015 Oh CW, Ivan D, Curry JL, Ellis R, Gerber H, Duvic M, et al: A case of indeterminate dendritic cell tumor presenting with leonine facies. J Cutan Pathol 43:158-163, 2016 Rezk SA, Spagnolo DV, Brynes RK, Weiss LM: Indeterminate cell tumor: a rare dendritic neoplasm. Am J Surg Pathol 32:1868-1876, 2008 Rodriguez-Jurado R, Vidaurri-de la Cruz H, Duran-Mckinster C, Ruiz-Maldonado R: Indeterminate cell histiocytosis. Clinical and pathologic study in a pediatric patient. Arch Pathol Lab Med 127:748-751, 2003 Roh J, Kim SW, Park CS: Indeterminate Dendritic Cell Tumor: A Case Report of a Rare Langerhans Cell Lineage Disease. J Pathol Transl Med 50:78-81, 2016 Rowden G, Phillips TM, Lewis MG: Ia antigens on indeterminate cells of the epidermis: immunoelectronmicroscopic studies of surface antigens. Br J Dermatol 100:531-542, 1979 Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al: The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127:2375-2390, 2016 Takahara K, Omatsu Y, Yashima Y, Maeda Y, Tanaka S, Iyoda T, et al: Identification and expression of mouse Langerin (CD207) in dendritic cells. Int Immunol 14:433-444, 2002 Weitzman S, Jaffe R: Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses. Pediatr Blood Cancer 45:256-264, 2005
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1.
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ACCEPTED MANUSCRIPT S.K. Tan et al. FIGURE LEGENDS: Fig. 1: MRI of thoracic spine revealing a 3-cm lesion (arrow) in the T9 vertebral body causing
Fig. 2: Cancellous bone destroyed by cellular infiltrate.
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retropulsion and compression of central canal.
Fig. 3: Tumor cells have irregular nuclear contours and abundant eosinophilic cytoplasm.
Fig. 5: Many tumor cells express CD1a. Fig. 6: Postoperative radiograph demonstrating AP view.
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Fig. 4: Aggregate of tumor cells with surrounding lymphocytes.
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Fig. 7: Postoperative radiograph demonstrating lateral view.
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Fig. 8: Postoperative CT scan of thoracic spine shows stable spinal implants and fusion.
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ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlight We reported the first case of spinal IDCT.
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SC
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•
ACCEPTED MANUSCRIPT
•
FISH: Fluorescence in situ hybridization
•
H&E: Hematoxilin and eosin
•
IDCT: Indeterminate dendritic cell tumor
•
LCH: Langerhans cell histiocytosis
•
MRI: Magnetic resonance imaging
•
NLCH: Non-Langerhans cell histiocytosis
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DC: Dendritic cells
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•
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Abbreviations and Acronyms:
ACCEPTED MANUSCRIPT
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Dear Editors,
Please review this submission for consideration of publication in World Neurosurgery. Each of the authors were closely involved in the production of this manuscript. There
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are no conflicts of interest associated with the generation of this manuscript. No
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financial support or grants are associated with this submission. The authors have adhered to the highest of ethical standards in the generation of this work.
Sincerely,
Lee Onn Chieng BS S z e K i a t T a n BS
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Ian Cote MD
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Karthik Madhavan MD
S1878-8750(17)31176-2
DOI:
10.1016/j.wneu.2017.07.076
Reference:
WNEU 6138
To appear in:
World Neurosurgery
Received Date: 20 March 2017 Revised Date:
12 July 2017
Accepted Date: 13 July 2017
Please cite this article as: Tan SK, Chieng LO, Madhavan K, Rosenberg A, Cote I, Indeterminate Dendritic Cell Tumor in Thoracic Spine: A Case Report and Review of Literature, World Neurosurgery (2017), doi: 10.1016/j.wneu.2017.07.076. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT S.K. Tan et al. Indeterminate Dendritic Cell Tumor in Thoracic Spine: A Case Report and Review of Literature
Cote, MD1
Department of Neurological Surgery
SC
1
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Sze Kiat Tan, BS1, Lee Onn Chieng, BS1, Karthik Madhavan, MD1, Andrew Rosenberg, MD2, Ian
and the Miami Project to Cure Paralysis Department of Pathology
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2
University of Miami Miller School of Medicine Miami, Florida, USA.
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Authors’ emails: Sze Kiat Tan – [email protected]
Lee Onn Chieng – [email protected]
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Karthik Madhavan – [email protected] Andrew Rosenberg – [email protected]
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Ian Cote – [email protected]
Corresponding author: Ian Cote MD
University of Miami MILLER School of Medicine Department of Neurological Surgery
1
ACCEPTED MANUSCRIPT S.K. Tan et al. Lois Pope Life Center 1095 NW 14th Terrace (D4-6)
305-256-4492
Fax:
305-243-3337
Email:
[email protected]
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Telephone:
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Miami, FL 33136
Keywords: Birbeck granules
•
Epidermotropism
•
Histiocytic sarcoma
•
Indeterminate dendritic cell tumor
•
Langerin
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•
Abbreviations and Acronyms: DC: Dendritic cells
•
FISH: Fluorescence in situ hybridization
• •
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•
EP
•
H&E: Hematoxilin and eosin IDCT: Indeterminate dendritic cell tumor LCH: Langerhans cell histiocytosis
•
MRI: Magnetic resonance imaging
•
NLCH: Non-Langerhans cell histiocytosis
Running title – Indeterminate Dendritic Cell Tumor
2
ACCEPTED MANUSCRIPT S.K. Tan et al. Abstract Indeterminate dendritic cell tumor (IDCT) is an extremely rare hematological disorder with poorly understood pathogenesis. Occasionally encountered by hematologists, unusual
RI PT
presentations of IDCT have never been reported in the spine literature. The authors report a case of a 51-year-old man who presented with progressively worsening axial thoracic back pain radiating to his sides for three months. MRI revealed a large 3-cm enhancing mass at the T9
SC
vertebral body with an exophytic component causing significant canal stenosis. Initial percutaneous biopsy revealed histiocytic sarcoma. The patient underwent exploratory
M AN U
throracotomy and en-bloc resection of the lesion with T8-10 fusion. Interestingly, the final pathology results revealed IDCT with fibrosis. IDCT immunostaining was partially positive for Langerhans cell marker (positive for S100 and CD1a, but lacked Birbeck granules and Langerin stain) and partially for blastic plasmacytoid dendritic cell neoplasm. In addition, it was positive
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for CD45, CD68 and CD163. Lymphadenopathy is absent in this patient. Although first reported in the 1980s, IDCT has been omitted from most classifications due to its rarity. Rezk et al. (2008), reported 5 cases of IDCT which is usually restricted to the skin and lymph nodes and
EP
carried a good prognosis. Hematologists have debated the cell of origin; it is believed to be comprised of pre-Langerhans cells, as Birbeck granules are acquired after migration to the
AC C
epidermis. As for now, IDCT remains of indeterminate origin. We report the first case of spinal IDCT, and familiarity with the histological features are warranted to ensure accurate diagnosis and appropriate treatment.
3
ACCEPTED MANUSCRIPT S.K. Tan et al. INTRODUCTION Indeterminate dendritic cell tumor (IDCT), comprised of so-called dermal indeterminate cells, is an extraordinary rare hematological neoplastic disorder.5,7 First noted by Wood et al. in 1985, it
RI PT
is an altered homing mechanism of proliferation of antigen-presenting dendritic cells.5 Due to its rarity, the proposed etiology of IDCT is unknown, although the most frequently discussed possibilities are extrinsic stimulations and association with low grade B-cell lymphoproliferative
SC
disorder.3,5 The pathophysiology has not been completely understood and hence often leads to
M AN U
misdiagnosis.
IDCT can develop in any population with no particular predilection for certain age or gender.7 The most common area of presentation of IDCT is usually skin, because these cells predominantly reside in the skin and lymph nodes.6 The skin of trunk and extremities are usually
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affected.4 There are three main types of dendritic cells (DC) in the human body that have been described, namely dermal DC expressing CD1a, dermal DC expressing CD14 and Langerhans cells expressing CD1a.4 Originating from the same progenitor cell, Rowden et al. suggested that
EP
indeterminate cells are pre-Langerhans cells that fail to complete their acquisition of Birbeck granules while migrating towards epidermis.8 Therefore, the major difference between these
AC C
dendritic cells is the presence of ultrastructure Birbeck granules in the IDCT cells.5 In addition, IDCT cells will stain CD1a and S-100 protein but not CD207 (langerin) immunohistologically.5
We describe our experience with the management of a case of IDCT in the thoracic spine, as compared to skin and lymph nodes cases that are often found in the past literature. This is
4
ACCEPTED MANUSCRIPT S.K. Tan et al. essential in spinal surgery as the familiarity with the histological features are warranted to ensure
RI PT
accurate diagnosis and appropriate treatment of this rare entity.
CASE REPORT History and Examination
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A 51-year-old man presented with progressively worsening axial thoracic back pain radiating to his sides for three months. The pain was not associated with paresthesia or weakness. Patient
M AN U
denied any cutaneous or systemic symptoms. There was no lymphadenopathy noted. Extensive serological laboratory workups of patient were normal.
Imaging Studies
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Magnetic resonance imaging (MRI) revealed a large 3-cm enhancing mass at the T9 vertebral body with an exophytic component causing significant canal stenosis with epidural extension (Fig. 1). A CT angiogram of the chest showed the presence of an artery of Adamkiewicz at the
EP
level of the lesion. Subsequent PET scan of whole body confirmed low-level FDG avid bilateral cervical subcentimeter nodes, likely reactive. Initial percutaneous needle biopsy showed
AC C
histiocytic sarcoma.
Operation
The patient underwent a right exploratory thoracotomy and en-bloc resection of the lesion with T8-10 posterolateral instrumented fusion using expandable titanium cage and rib autograft. 7th rib is also partially resected.
5
ACCEPTED MANUSCRIPT S.K. Tan et al. Pathological Examination The histopathological examination of the 4.5 × 3.7 × 2.1-cm resected mass revealed indeterminate dendritic cell tumor with fibrosis, chronic inflammation and reactive woven bone
RI PT
formation. The mass was an irregularly shaped lytic tumor-like lesion with no clear laterality. It mainly involved the middle as well as posterior aspects of the vertebral body, and extended through the cortex into the adjacent soft tissues. All inked resection margins were negative, and
SC
the clearance to the closest soft tissue margin was less than 0.1cm.
M AN U
The neoplasm was unusual and was composed of a multinodular proliferation of large histiocytelike cells with hyperlobulated nuclei that had smooth to irregular contours (Fig. 2 and 3). The cytoplasm of tumor cells was eosinophilic and abundant. The tumor cells demonstrated limited cytologic atypia, minimal mitotic activity and no necrosis. The lesional cells were admixed with
4).
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macrophages with significant lymphoblastic infiltration and surrounded by reactive fibrosis (Fig.
EP
Immunohistochemistry shows that the lesion cells are positive for CD1a, CD45, CD68 and CD163 (pale), and focally express Oct 2 (dim nuclear staining) as well as S100 (Fig. 5). The
AC C
cells stained negative for Langerin, CD30, CD3, CD20, CD21, CD23, CD35, kappa and lambda light chains, tryptase, keratin, CK8/18, EMA, SALL4, BRAF and desmin. The proliferation rate estimated from the Ki67 stain is low and is less than 2%. This staining pattern is very consistent with an indeterminate dendritic cell tumor. Having abundant tissues to examine this time, the interpretation of malignancy was not warranted although the initial needle percutaneous biopsy was interpreted as representing histiocytic sarcoma.
6
ACCEPTED MANUSCRIPT S.K. Tan et al.
Postoperative Course The patient’s immediate
postoperative neurological examination remained unchanged. He
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recovered uneventfully and was discharged to home on postoperative day 12. On the third month post-operation, he continued to be symptoms free and the postoperative X-ray and CT
SC
demonstrated stable spinal construct and arthrodesis (Fig. 6, 7 and 8).
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DISCUSSION
To our best knowledge, this is the first reported case of IDCT in the spine as it usually presents as cutaneous neoplasm with multiple disseminated papules, nodules or plaques on skin in the absence of clinical manifestations.1,5 In the 2016 World Health Organization (WHO)
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Classification of Neoplasms of the Hematopoietic and Lymphoid tissues, nine types of dendritic cell neoplasms are listed: histiocytic sarcoma, Langerhans cell histiocytosis (LCH), Langerhans cell sarcoma, IDCT, follicular dendritic cell sarcoma, interdigitating dendritic cell sarcoma,
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fibroblastic reticular cell tumor, disseminated juvenile xanthogranuloma and Erdheim-Chester disease.9 On the other hand, Oh et al. described another classification of cutaneous histiocytic
AC C
proliferation based on the immunophenotypic characteristics of lesional cells, namely “factor XIIIa-CD68+CD163+ macrophage, factor XIIIa+CD68+S100-CD1a- dermal dendritic cells, factor XIIIa-S100+CD1a+ LCs with Birbeck granules, and factor XIIIa-S100+CD1a+ indeterminate cells without Birbeck granules”.4
7
ACCEPTED MANUSCRIPT S.K. Tan et al. IDCT cells are hypothesized to belong to the family of myeloid cells.5 This is supported by the reported cases of antecedent as well as concurrent low-grade B-cell lymphoma in some patients.5 It is of interest to note that fluorescence in situ hybridization (FISH) demonstrated that both
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histiocytic/dendritic neoplasm and B-cell lymphoma express identical heavy chain gene rearrangements.5 The myeloid cells can differentiate through either antigen-presenting pathway or antigen-processing pathway to become colony-forming unit (CFU)-granulocytic/monocytic
SC
cells and CFU-dendritic cells respectively depending on the presence of specific cytokines.5 Langerhans cells and interstitial dendritic cells are later developed from the immature dendritic
M AN U
cells.5
Due to the unclear pathobiology of IDCT and its similarity to LCH, it is essential to be able to differentiate these diseases and treat them accordingly. Morphologically, IDCT cells possess
TE D
long dendritic processes that are interdigitating with the processes of other IDCT cells.5 They also contain a high number of cytoplasmic organelles, but not Birbeck granules. In 1961, Birbeck et al. first reported this “tennis-racket” appearance organelles under the electron microscope that
EP
play a significant role in endocytosis.10 Langerin is a type II membrane-associated C-type lectin that is closely related to the Birbeck granules.2,10 It is also postulated that the IDCT cells are pre-
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Langerhans cells and they are arrested before acquisition of Birbeck granules during their transition from dermal to epidermal regions, possibly after their cell receptors interact with an epidermis-specific ligand.1,5 Therefore, the immunostaining for CD1a, CD68 and S100 are positive in both IDCT and Langerhans cells, but negative for CD207 in IDCT cells.5 This is the main characteristic that is used in diagnosis to distinguish between IDCT cells and Langerhans cells. On the other hand, non-Langerhans cell neoplasms (NLCN) such as Rosai-Dorfman
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ACCEPTED MANUSCRIPT S.K. Tan et al. disease, juvenile xanthrogranuloma, multicentric reticulohistiocytosis, histiocytic sarcoma and Erdheim-Chester disease do not show the uniform expression of both S100 protein and CD1a.7,11
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Furthermore, CD1a is weakly and only focally expressed in NLCN.1
As compared to Langerhans cells, IDCT lesional cells usually lack of eosinophils and epidermotropism with microabscesses that are more typical for LCH.5 Hematoxilin and eosin
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(H&E) stain is unable to differentiate between these cells because of their close resemblance. Thus, the use of immunohistochemistry and electron microscope for the confirmation of IDCT
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and LCH is widely utilized, and remains the only modality to differentiate the two.
No standardized therapeutic regimen has been established for patients with IDCT. For cutaneous IDCT with single lesion, total resection by surgery is usually recommended.3 However, systemic
fluorouracil,
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treatment such as electron beam therapy, narrow-band ultraviolet, electrodessication, topical 5thalidomide, and low dose methotrexate have been suggested for those who
presented with generalized skin lesions.1,3 5% pure coal tar is also effective in pediatric patient.6
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There are also reported cases of spontaneous self-regression without treatment.3 The close follow-up of cases has found that the clinical course of IDCT is very indolent and usually self-
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limiting.3
It is extremely important to include LCH and Langerhans cell sarcoma in the differential diagnosis during the work-up. The ability to distinguish these entities is vital, as erroneously identifying IDCT as LCH can lead to overly aggressive management when more conservative measures are sufficient. The prognosis of IDCT is variable.3 Although in rare cases it can
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ACCEPTED MANUSCRIPT S.K. Tan et al. progress to leukemia, there is no mortality case due to IDCT so far.6,7 In our case, surgical removal of the tumor is still deemed to be the best option for our patient even though the final
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diagnosis of IDCT was only discovered after resection of tumor mass.
In summary, IDCT is an extraordinarily rare malignancy that tends to be neglected in differential because of that. This is essential in spinal surgery as the familiarity with the histological features
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is warranted to ensure accurate diagnosis and appropriate treatment. Langerin (CD207) immunonegativity and the absence of Birbeck granules on electron microscopy for definite
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diagnosis must be shown, and the patient needs to be monitored closely with follow-ups.7
Conflict of interest statement: The authors report no conflicts of interest concerning the materials or methods used in this study or the findings specified in this paper.
Acknowledgements: No
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ACCEPTED MANUSCRIPT S.K. Tan et al. REFERENCES:
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Bakry OA, Samaka RM, Kandil MA, Younes SF: Indeterminate cell histiocytosis with naive cells. Rare Tumors 5:e13, 2013 Mizumoto N, Takashima A: CD1a and langerin: acting as more than Langerhans cell markers. J Clin Invest 113:658-660, 2004 Mo X, Guo W, Ye H: Primary Indeterminate Dendritic Cell Tumor of Skin Correlated to Mosquito Bite. Medicine (Baltimore) 94:e1443, 2015 Oh CW, Ivan D, Curry JL, Ellis R, Gerber H, Duvic M, et al: A case of indeterminate dendritic cell tumor presenting with leonine facies. J Cutan Pathol 43:158-163, 2016 Rezk SA, Spagnolo DV, Brynes RK, Weiss LM: Indeterminate cell tumor: a rare dendritic neoplasm. Am J Surg Pathol 32:1868-1876, 2008 Rodriguez-Jurado R, Vidaurri-de la Cruz H, Duran-Mckinster C, Ruiz-Maldonado R: Indeterminate cell histiocytosis. Clinical and pathologic study in a pediatric patient. Arch Pathol Lab Med 127:748-751, 2003 Roh J, Kim SW, Park CS: Indeterminate Dendritic Cell Tumor: A Case Report of a Rare Langerhans Cell Lineage Disease. J Pathol Transl Med 50:78-81, 2016 Rowden G, Phillips TM, Lewis MG: Ia antigens on indeterminate cells of the epidermis: immunoelectronmicroscopic studies of surface antigens. Br J Dermatol 100:531-542, 1979 Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al: The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127:2375-2390, 2016 Takahara K, Omatsu Y, Yashima Y, Maeda Y, Tanaka S, Iyoda T, et al: Identification and expression of mouse Langerin (CD207) in dendritic cells. Int Immunol 14:433-444, 2002 Weitzman S, Jaffe R: Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses. Pediatr Blood Cancer 45:256-264, 2005
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1.
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ACCEPTED MANUSCRIPT S.K. Tan et al. FIGURE LEGENDS: Fig. 1: MRI of thoracic spine revealing a 3-cm lesion (arrow) in the T9 vertebral body causing
Fig. 2: Cancellous bone destroyed by cellular infiltrate.
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retropulsion and compression of central canal.
Fig. 3: Tumor cells have irregular nuclear contours and abundant eosinophilic cytoplasm.
Fig. 5: Many tumor cells express CD1a. Fig. 6: Postoperative radiograph demonstrating AP view.
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Fig. 4: Aggregate of tumor cells with surrounding lymphocytes.
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Fig. 7: Postoperative radiograph demonstrating lateral view.
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Fig. 8: Postoperative CT scan of thoracic spine shows stable spinal implants and fusion.
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Highlight We reported the first case of spinal IDCT.
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FISH: Fluorescence in situ hybridization
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H&E: Hematoxilin and eosin
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IDCT: Indeterminate dendritic cell tumor
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LCH: Langerhans cell histiocytosis
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MRI: Magnetic resonance imaging
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NLCH: Non-Langerhans cell histiocytosis
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DC: Dendritic cells
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Abbreviations and Acronyms:
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Dear Editors,
Please review this submission for consideration of publication in World Neurosurgery. Each of the authors were closely involved in the production of this manuscript. There
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are no conflicts of interest associated with the generation of this manuscript. No
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financial support or grants are associated with this submission. The authors have adhered to the highest of ethical standards in the generation of this work.
Sincerely,
Lee Onn Chieng BS S z e K i a t T a n BS
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Ian Cote MD
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Karthik Madhavan MD