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 Table of Contents  
Year : 2021  |  Volume : 16  |  Issue : 1  |  Page : 89-92

A case of juvenile lupus with an extremely rare dendritic cell malignancy: Interdigitating dendritic cell sarcoma – coexistence or paraneoplastic manifestation?

1 Department of Clinical Immunology and Rheumatology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
3 Department of Medical Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India

Date of Web Publication23-Mar-2021

Correspondence Address:
Dr. Pratyusha Rajavarapu
Flat Number 303, Sai Mitra Legacy, Kamalapuri Colony Phase II, Srinagar Colony, Hyderabad - 500 073, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_124_19

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Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, characterized by circulating autoantibodies, widespread inflammation, and tissue destruction. The association between cancer and SLE is intriguing in view of their common pathophysiological pathways. It is established that there is an increased risk for overall malignancies in SLE, with standardized incidence ratios ranging from 1.14 to 3.6. Hematological malignancies are more common than solid organ malignancies in SLE. Malignancy when associated with lupus usually follows the diagnosis, but can occur concurrently or even predate the diagnosis of SLE. Neoplasms of dendritic cells (DCs), the key antigen-presenting cells, are rare, and they account for <1% of all lymph node tumors. Interdigitating DC sarcoma (IDCS) is a rare hematological malignancy of DCs, with only a few over 100 cases being reported in literature. IDCS is usually seen in elderly males in their sixth decade. Here, we report a rare case of SLE and IDCS occurring together in a 5-year-old girl. The persistence of lymphadenopathy despite improvement in other lupus-specific features following the initiation of treatment led to a suspicion of malignancy which was proven on histopathology. Another unique feature of our case was that remission and relapse of both SLE and IDCS occurred synchronously. Although this presentation is rare, clinicians must be aware of the possibility of SLE and malignancies occurring together, especially in the presence of atypical clinical manifestations such as persistent lymphadenopathy. This knowledge helps in early diagnosis and effective treatment of both these conditions.

Keywords: Interdigitating dendritic cell sarcoma, juvenile systemic lupus erythematosus, paraneoplastic lupus erythematosus, S100

How to cite this article:
Rajavarapu P, Ponnuru D, Uppin M, Konatam ML, Kumar D P, Rajasekhar L. A case of juvenile lupus with an extremely rare dendritic cell malignancy: Interdigitating dendritic cell sarcoma – coexistence or paraneoplastic manifestation?. Indian J Rheumatol 2021;16:89-92

How to cite this URL:
Rajavarapu P, Ponnuru D, Uppin M, Konatam ML, Kumar D P, Rajasekhar L. A case of juvenile lupus with an extremely rare dendritic cell malignancy: Interdigitating dendritic cell sarcoma – coexistence or paraneoplastic manifestation?. Indian J Rheumatol [serial online] 2021 [cited 2021 Dec 2];16:89-92. Available from:

  Introduction Top

Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disease predominantly affecting young women. Many studies documented increased risk of malignancy, especially hematological in SLE.[1] Neoplasms of dendritic cells (DCs), the key antigen-presenting cells, are rare, and they account for <1% of all lymph node tumors. Among them, interdigitating DC sarcoma (IDCS) is a less common subtype and its diagnosis is based on immunohistochemistry (IHC) studies.[2] Its association with SLE has not been previously reported.

  Case Report Top

A 5-year-old girl presented with a 3½-month history of high-grade intermittent fever and erythematous maculopapular rashes over both the upper and lower limbs [Figure 1], following which she developed inflammatory arthritis involving both knees and ankles. On examination, she had significant bilateral cervical, axillary, and inguinal lymphadenopathy and mild hepatosplenomegaly. Initial lymph node biopsy was suggestive of reactive follicular hyperplasia without evidence of malignancy. Blood investigations revealed positive anti-nuclear autoantibody (ANA) on immunofluorescence with 4+ (Speckled) pattern in a dilution of 1:100, dsDNA positive (2.1 [<0.9] by enzyme-linked immunosorbent assay method), and hypocomplementemia (C3 of 14 [<90] mg/dl and C4 of 1 [<10] mg/dl by nephelometry), fulfilling the SLICC 2012 SLE criteria, and was started on 5 mg of prednisolone and hydroxychloroquine.
Figure 1: Rash over both the lower limbs

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Over the next 2 months, she had improvement in fever, arthritis of upper and lower limbs, and maculopapular rash, but lymphadenopathy persisted and increased in size. Repeat lymph node biopsy was done, and this time, it revealed complete effacement of the architecture. There were spindle cells with elongated vesicular folded nuclei arranged in fascicles and whorling pattern and mild cellular pleomorphism with occasional mitosis. The spindle cells showed intense IHC positivity for S100. The other IHC markers including CD1a, CD30, CD21, CD35, CD20, and pancytokeratin were negative. The morphologic and IHC features were consistent with the diagnosis of IDCS [Figure 2].
Figure 2: (a and b) Section from the lymph node showing effacement of the architecture and the cells arranged in short fascicles in the medulla. (c) The cells were polygonal to spindle shaped with vesicular nuclei and atypia (H and E, ×400). (d) Immunohistochemistry with S-100 showing intense positivity in these cells

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Computed tomography (CT) imaging showed enlarged bilateral axillary, posterior mediastinal (1.4 cm × 2 cm × 4.3 cm), and para-aortic lymph nodes. Medical oncology consultation was taken, and she was started on ABVD regimen of chemotherapy. Remission was documented at the end of six cycles, with repeat lymph node biopsy showing only reactive hyperplasia without any evidence of residual tumor and positron emission tomography-CT showing low to no uptake in the spleen and lymph nodes, with regression of lymph nodal size. Chemotherapy was stopped, and she was asymptomatic.

Two months later, she again developed low-grade fever, arthritis, and maculopapular rash over both the legs along with relapse of lymphadenopathy. Her investigations were again showing high titers of dsDNA antibodies 2.3 (<0.9), hypocomplementemia, and proteinuria (24-h urinary protein of 700 mg) with no active sediment. She also had severe colicky left hypochondriac pain, and CT abdomen revealed multiple enlarged abdominal lymph nodes. Repeat cervical node biopsy showed a relapse of IDCS. The patient is currently undergoing the fifth cycle of chemotherapy. She had improvement in rashes, arthritis, fever, and proteinuria, also following the initiation of chemotherapy, this time with iphosphomide, carboplatin, and etoposide regimen.

  Discussion Top

Systemic lupus erythematosus and malignancy

In addition to renal injury and infection, malignancy is known to be a significant cause of death in SLE. Lupus patients have a slightly higher overall malignancy risk with standardized incidence ratios (SIRs) of 1.14–3.6. This risk could be explained by the common immune and genetic pathways underlying the pathogenesis of SLE and malignancy.[1] Autoantibodies seen in SLE can alter DNA repair and lead to the accumulation of DNA damage, which increases the risk of cancer. Examples of such antibodies include anti3E10.[3] Anticardiolipin antibodies were also a risk factor for malignancy.[4] The cytokines, BAFF, and APRIL, responsible for the survival and proliferation of B cells, are overexpressed in both SLE and non-Hodgkin lymphoma (NHL) (particularly diffuse large B-cell lymphoma [DLBCL]). These cytokines can cause overstimulation and aberrant activation of B cells culminating in mutagenesis.[5] Further, immunosuppressant drugs (ISDs) may mediate the development of malignancy by causing alteration in the immune cells through mutagenesis and cytotoxicity. ISDs can also result in decreased clearance or increased susceptibility to oncogenic viruses, especially human papillomavirus. Owing to the fact that patients who are on higher immunosuppressive treatment also have higher disease activity, it is difficult to establish the exact etiological role of ISDs in cancer development.[1],[6]

Hematological malignancies, particularly lymphomas, are more commonly associated with lupus than solid organ malignancies. In a meta-analysis by Apor et al.,[7] including 67,929 patients from eight cohort studies, there was 2.9-fold increase (95% confidence interval [CI]: 2.0–4.4) in the incidence of all hematologic malignancies in lupus patients. In a meta-analysis, Cao et al.[8] demonstrated an increased incidence of NHL with pooled relative risks of 5.40 (95% CI: 3.75–7.77) (most common being DLBCL), 3.26 (95% CI: 2.17–4.88) for Hodgkin's lymphoma, and 2.01 (95% CI: 1.61–2.52) for leukemia.

Malignancy in juvenile SLE was less extensively studied. In a cohort study including data from 12 pediatric rheumatology clinics in North America, 1168 patients were followed up for 7.6 years (interquartile range 3.4–10). Among them, 14 invasive cancers occurred, producing an SIR of 4.13 (95% CI: 2.26–6.93). Of them, three were NHL; two were head-and-neck squamous cell carcinomas (tongue and nasopharynx); and one each of glioblastoma, thyroid papillary adenoma, breast cancer, and adenocarcinoma not otherwise specified; and three cancers whose morphology and histology codes were indeterminate.[9]

In a recent large meta-analysis of 96,578 patients from 25 adult case series and 5 pediatric case series comparing malignancy rates in adult- and childhood-onset SLE, cancer incidence was lower in childhood-onset SLE (0.5%, 95% CI: 0.03%–1.5%) versus adult-onset SLE (4.2%, 95% CI: 3.2%–5.3%). They found a bimodal pattern to the onset of hematologic malignancies in juvenile SLE, with younger children having a higher risk of leukemia and older children of lymphoma.[10] Most of the data show that malignancy is detected after the diagnosis and treatment of SLE. However, one study assessing the hematological malignancy incidence in SLE described that nearly one-third of the patients were diagnosed earlier or concurrently with a diagnosis of malignancy. Such patients were found to have a better outcome pertaining to malignancy.[11]

Another area of interest is SLE presenting as a paraneoplastic manifestation. Paraneoplastic symptoms are caused by a malignancy, but not directly related to invasion by the tumor or its metastases, and are the result of a wide variety of tumor-derived biologic mediators such as hormones, peptides, antibodies, cytotoxic lymphocytes, and autocrine and paracrine mediators. Inflammatory myopathies, seronegative rheumatoid arthritis, and atypical vasculitides are frequently reported paraneoplastic rheumatic diseases, and paraneoplastic lupus-like (pLE) syndromes are less common.[12] About 33 cases of pLE were reported till date, associated with solid organ malignancies such as lung, breast carcinoma, and hematological malignancies such as acute myeloid leukemia.[13] The most common presentations in pLE were subacute cutaneous lupus, serositis, Raynaud's phenomenon, and ANA and anti-dsDNA antibody positivity. Owing to the close temporal relation between the onset and flare of both lupus and IDCS, in this case, a differential of pLE could be considered. However, the complete clinical picture of SLE, particularly with hypocomplementemia and nephritis as seen here, is rare.

Interdigitating dendritic cell sarcoma: A brief review

Peripheral lymphoid organs contain a group of structural and immune accessory cells called reticulum cells. They constitute a minor fraction in these organs and encompass different types of DCs.[14] The following four types of DCs exist in lymph nodes: follicular DC (FDC), interdigitating DCs (IDCs), Langerhans, and histolytic/fibroblastic cells. FDCs are localized to the germinal center and present antigens to B cells, whereas IDCs are localized to the paracortex of lymph nodes and the periarteriolar lymphoid sheaths in the spleen and present antigens to T cells.[15] DC neoplasms are uncommon, and the WHO has classified them into the following five groups: Langerhans cell histiocytosis, Langerhans cell sarcoma, IDCS, FDC sarcoma, and not specified otherwise.[2]

Among them, FDC sarcoma is the most common type followed by IDCS. A recent pooled analysis of 462 cases of DC sarcomas showed that only 100 cases of IDCS were reported. It was the most aggressive form among all, and the median age at diagnosis was 56.5 (1.8–88) years with a male predominance (1.38:1). Painless lump in cervical or axillary areas was the most common presentation. Fever, weight loss, night sweats, and fatigue have been reported. Isolated nodal disease (47%) involving the cervical area was most common, followed by combined nodal and extranodal involvement (28%) and isolated extranodal disease (25%), with liver being the most common extranodal site involved. Patients with gastrointestinal involvement presented with intestinal obstruction, abdominal pain, or dyspepsia.[14]

Diagnosis of IDCS can be challenging because of its rarity and morphologic similarity to many of the spindle cell neoplasms involving lymph nodes. Microscopically, IDCS has large fusiform spindle cells with storiform or whorled growth pattern with small nucleoli resembling histiocytes. The presence of small lymphocytes intermingling with large histiocytic cell population is a key diagnostic feature of IDCS, which differentiates it from carcinomas, lymphomas, and sarcomas, which are the closest differentials histologically.[16] In IDCS, IHC plays a crucial role which is characterized by positive staining for S-100, vimentin, human leukocyte antigen-antigen D related or CD-68, and leukocyte common antigen and negative staining for CD1a, CD21, CD35, CD30, CD20, cytokeratin (CK), myeloperoxidase, and langerin.[15] In our case, staining for S-100 was positive, but CD1a, CD21, CD30, and Pan CK were negative, thus confirming the diagnosis.

The etiopathogenesis of IDCS is unknown. Epstein–Barr virus has been suggested as a causative factor in the development of FDC sarcomas, but not IDCS. However, the association of IDCS with preceding or concomitant malignant neoplasms has been suggested in case reports.[17] Saygin et al. reported concurrence rates of 12% with hematopoietic and up to 9% with solid organ malignancies, in patients with IDCS during their lifetime. This high frequency may be related to aging, or may support the hypothesis that DCs introduce tumor antigens to immune cells and that their dysfunction could result in a diminished response to the neoplasm.[14] Interestingly, there were three case reports of development of IDCS following topical and systemic therapy with calcinuerin inhibitors, given for eczema, seborrheic dermatitis, and following liver transplant. These drugs dampen the response of T cells to which IDCs present antigens. Thus, dysregulation of immune system may facilitate malignant transformation of IDCs, but further data are required to elucidate it.[18],[19]

  Conclusion Top

We report a case of juvenile SLE coexistent with an extremely rare DC malignancy. IDCS occurred very early in the disease course and relapse of the malignancy was associated with flare of the disease. Although DCs were proven to have a role in the pathogenesis of development of lupus, no association between IDCS and lupus has been reported previously.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that the child's name and initial will not be published, and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Choi MY, Flood K, Bernatsky S, Ramsey-Goldman R, Clarke AE. A review on SLE and malignancy. Best Pract Res Clin Rheumatol 2017;31:373-96.  Back to cited text no. 1
Pokuri VK, Merzianu M, Gandhi S, Baqai J, Loree TR, Bhat S. Interdigitating dendritic cell sarcoma. J Natl Compr Canc Netw 2015;13:128-32.  Back to cited text no. 2
Noble PW, Bernatsky S, Clarke AE, Isenberg DA, Ramsey-Goldman R, Hansen JE. DNA-damaging autoantibodies and cancer: The lupus butterfly theory. Nat Rev Rheumatol 2016;12:429-34.  Back to cited text no. 3
Gómez-Puerta JA, Cervera R, Espinosa G, Aguiló S, Bucciarelli S, Ramos-Casals M, et al. Antiphospholipid antibodies associated with malignancies: Clinical and pathological characteristics of 120 patients. Semin Arthritis Rheum 2006;35:322-32.  Back to cited text no. 4
Löfström B, Backlin C, Pettersson T, Lundberg IE, Baecklund E. Expression of APRIL in diffuse large B cell lymphomas from patients with systemic lupus erythematosus and rheumatoid arthritis. J Rheumatol 2011;38:1891-7.  Back to cited text no. 5
Bernatsky S, Ramsey-Goldman R, Joseph L, Boivin JF, Costenbader KH, Urowitz MB, et al. Lymphoma risk in systemic lupus: Effects of disease activity versus treatment. Ann Rheum Dis 2014;73:138-42.  Back to cited text no. 6
Apor E, O'Brien J, Stephen M, Castillo JJ. Systemic lupus erythematosus is associated with increased incidence of hematologic malignancies: A meta-analysis of prospective cohort studies. Leuk Res 2014;38:1067-71.  Back to cited text no. 7
Cao L, Tong H, Xu G, Liu P, Meng H, Wang J, et al. Systemic lupus erythematous and malignancy risk: A meta-analysis. PLoS One 2015;10:e0122964.  Back to cited text no. 8
Bernatsky S, Clarke AE, Zahedi Niaki O, Labrecque J, Schanberg LE, Silverman ED, et al. Malignancy in pediatric-onset systemic lupus erythematosus. J Rheumatol 2017;44:1484-6.  Back to cited text no. 9
Aoki PR, El Dib R, Silva CA, Magalhaes CS. Description of Malignancy Rates in Childhood- and Adult-Onset Systemic Lupus Erythematous by Proportional Meta-analysis. J Clin Rheumatol 2017;23:187-92.  Back to cited text no. 10
Knight JS, Blayney DW, Somers EC. Patients with systemic lupus erythematosus and haematological malignancy at a tertiary care centre: Timing, histopathology and therapy. Lupus Sci Med 2014;1:e000051.  Back to cited text no. 11
Racanelli V, Prete M, Minoia C, Favoino E, Perosa F. Rheumatic disorders as paraneoplastic syndromes. Autoimmun Rev 2008;7:352-8.  Back to cited text no. 12
Mostmans Y, Grosber M, De Coninck A, Peeters V, Ring J, Gutermuth J. Paraneoplastic systemic lupus erythematosus in association with oat cell tumour of the lung. J Eur Acad Dermatol Venereol 2018;32:e25-6.  Back to cited text no. 13
Saygin C, Uzunaslan D, Ozguroglu M, Senocak M, Tuzuner N. Dendritic cell sarcoma: A pooled analysis including 462 cases with presentation of our case series. Crit Rev Oncol Hematol 2013;88:253-71.  Back to cited text no. 14
Kairouz S, Hashash J, Kabbara W, McHayleh W, Tabbara IA. Dendritic cell neoplasms: An overview. Am J Hematol 2007;82:924-8.  Back to cited text no. 15
Ylagan LR, Bartlett NL, Kraus M. Interdigitating dendritic reticulum cell tumor of lymph nodes: Case report with differential diagnostic considerations. Diagn Cytopathol 2003;28:278-81.  Back to cited text no. 16
Vasef MA, Zaatari GS, Chan WC, Sun NC, Weiss LM, Brynes RK. Dendritic cell tumors associated with low-grade B-cell malignancies. Report of three cases. Am J Clin Pathol 1995;104:696-701.  Back to cited text no. 17
Gordon MK, Kraus M, van Besien K. Interdigitating dendritic cell tumors in two patients exposed to topical calcineurin inhibitors. Leuk Lymphoma 2007;48:816-8.  Back to cited text no. 18
Wu Q, Liu C, Lei L, Yan X, Wang B, Liu X, et al. Interdigitating dendritic cell sarcoma involving bone marrow in a liver transplant recipient. Transplant Proc 2010;42:1963-6.  Back to cited text no. 19


  [Figure 1], [Figure 2]


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